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 ◽  
...  

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.

Author(s):  
Sheridan Joseph ◽  
Timothy J. Whitman ◽  
Frederick S. Buckner ◽  
Anna L. Cogen

Cutaneous leishmaniasis (CL) is often caused by Leishmania braziliensis (L. braziliensis) in South America. Because of the risk for mucocutaneous leishmaniasis, L. braziliensis is frequently treated with parenteral or oral medications. Here, we present a case of a young woman with L. braziliensis (CL) that did not respond to miltefosine but eventually experienced spontaneous resolution. This case highlights the potential for treatment failure and the importance of clinical monitoring in the setting of cutaneous leishmaniasis caused by L. braziliensis.


2020 ◽  
Vol 11 ◽  
Author(s):  
Fernando Torres ◽  
Sara M. Robledo ◽  
Wiston Quiñones ◽  
Gustavo Escobar ◽  
Rosendo Archbold ◽  
...  

Through bioguided in vitro assays, the leishmanicidal and trypanocidal effects of an ethanol extract, seven fractions, and two pure substances obtained from Clathrotropis brunnea Amshoff sawdust were established. The effectiveness of the two metabolites was confirmed in a hamster model of cutaneous Leishmaniasis by Leishmania braziliensis and in Balb/c mice infected by Trypanosoma cruzi. In vitro, 3,5-dimethoxystilbene was the most active against L. braziliensis amastigotes, with a median lethal concentration (LC50) of 4.18 μg/ml (17.40 μM) and a selectivity index of 3.55, but showed moderate activity for T. cruzi, with a median effective concentration (EC50) value of 27.7 μg/ml (115.36 μM). Flavanone pinostrobin, meanwhile, showed high activity against L. braziliensis, with an EC50 of 13.61 μg/ml (50.39 μM), as well as for T. cruzi, with an EC50 of 18.2 μg/ml (67.38 μM). The animal model assay of cutaneous Leishmaniasis showed that 50% of the hamsters treated with pinostrobin were definitively cured the cutaneous ulcer, and 40% showed an improvement, with a reduction in the size of the of 84–87%. Moreover, Balb/c mice experimentally infected with T. cruzi and treated for 25 days with pinostrobin experienced a reduction in their parasitemia by 71%. These results demonstrate the high potential of C. brunnea Amshoff against cutaneous Leishmaniasis and American trypanosomiasis and indicate the pharmacological potential of waste from the wood industry, which has tons of potentially useful chemicals for the development of new medicines.


2016 ◽  
Vol 61 (3) ◽  
Author(s):  
María del Mar Castro ◽  
Maria Adelaida Gomez ◽  
Anke E. Kip ◽  
Alexandra Cossio ◽  
Eduardo Ortiz ◽  
...  

ABSTRACT An open-label pharmacokinetics (PK) clinical trial was conducted to comparatively assess the PK and explore the pharmacodynamics (PD) of miltefosine in children and adults with cutaneous leishmaniasis (CL) in Colombia. Sixty patients, 30 children aged 2 to 12 years and 30 adults aged 18 to 60 years, were enrolled. Participants received miltefosine (Impavido) at a nominal dose of 2.5 mg/kg/day for 28 days. Miltefosine concentrations were measured in plasma and peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry of samples obtained during treatment and up to 6 months following completion of treatment, when therapeutic outcome was determined. Fifty-two patients were cured, 5 pediatric patients failed treatment, and 3 participants were lost to follow-up. Leishmania (Viannia) panamensis predominated among the strains isolated (42/46; 91%). Noncompartmental analysis demonstrated that plasma and intracellular miltefosine concentrations were, overall, lower in children than in adults. Exposure to miltefosine, estimated by area under the concentration-time curve and maximum concentration, was significantly lower in children in both the central and intracellular compartments (P < 0.01). Leishmania persistence was detected in 43% of study participants at the end of treatment and in 27% at 90 days after initiation of treatment. Clinical response was not dependent on parasite elimination. In vitro miltefosine susceptibility was similar for Leishmania strains from adults and children. Our results document PK differences for miltefosine in children and adults with cutaneous leishmaniasis that affect drug exposure and could influence the outcome of treatment, and they provide bases for optimizing therapeutic regimens for CL in pediatric populations. (This study has been registered at ClinicalTrials.gov under identifier NCT01462500.)


1904 ◽  
Vol 4 (1) ◽  
pp. 31-72 ◽  
Author(s):  
E. F. Bashford

By means of the graphic records given on Plates II–VI and VIII the following facts have been illustrated.Immunity to Erythrocytes.Normal rabbit's serum is relatively innocuous for bullock's erythrocytes. The serum of an immunised rabbit acquires the power to dissolve bullock's erythrocytes.Besides acquiring the power to dissolve bullock's erythrocytes, an immune serum may also acquire power to clump them, and it has been shown that the phenomena of haemolysis and of agglutination are independent.The powers acquired by the immune serum can be artificially modified. The serum may be deprived of its powers by heat. Serum cautiously so deprived of its haemolytic power can have it restored by the addition of normal serum. The haemolytic power of the un-heated serum is augmented if normal serum be superadded.It has been shown that an immune serum only differs from a normal serum by its containing antitoxic bodies which are endowed with powers of specific reaction with the bullock's erythrocytes.The mechanism by which erythrocytes are laked by an immune serum has been analysed, and it has been shown that the solution of the erythrocytes is effected through the intervention of an anti-erythrocytic body called forth by immunisation. The erythrocytes which have been subjected to the action of this product of immunity give indication of their reaction with it if they are subsequently or concomitantly placed under the influence of normal serum. The erythrocytes and normal serum together, therefore, form a combined indicator of the presence of the anti-eiythrocytic body. The part played by normal serum has nothing to do with the acquisition of immunity.The only conclusion drawn from the above observations is that in the production of immunity to erythrocytes the serum of the immunised animal acquires certain powers which are concomitant with, but are not necessarily the cause of the immunity. This special case of immunity to erythrocytes is therefore probably parallel to induced immunity to those bacterial toxines for which antitoxines are known to exist.The course and progressive augmentation of artificial immunity to erythrocytes has also been illustrated, and it has been shown that erythrocytes saturated with anti-erythrocytic body retain the power to augment the immunity of an already immune animal.The serum of an animal actively immunised has power to confer passive immunity upon other animals, and the course of this passive immunity differs in the two cases when it is induced in the same species and in a species alien to that providing the immune serum.The experiments with bullock's erythrocytes have been repeated in parallel observations with ricin in order to permit of the observations on haemolysis being utilised in drawing conclusions on the behaviour of bacterial toxines.By adjusting the conditions of experiment in such a way that the minimal lethal dose for an animal was also the minimal agglutinating dose in test-tube experiments, it has been possible to give graphic records showing the parallelism between the processes when erythrocytes or living animals are used as indicators of the presence of free ricin. In this way it has been possible to illustrate the determination of the minimal lethal and minimal agglutinating doses of ricin and that quantity of antitoxine (antiricin) which is necessary to abolish the corresponding actions in the animal and in the test-tube, and to show that the mixture of toxine and antitoxine which is physiologically neutral in vitro is also physiologically neutral in vivo within the limitations imposed by the preliminary determinations.The consequences of conferring passive immunity upon the guinea-pig by means of active immune serum of the rabbit have also been illustrated, and it has been shown that the alien antiricin serum leads to the production of agencies directed against itself.Ricin neutralised by antiricin retains its power to produce immunity when injected into the species of animal which has yielded the antiricin.In connection with the conference of immunity to erythrocytes and to ricin, the nature of the difference between normal and immune sera has been studied. Attention has been directed to the possession by normal sera of properties which simulate those possessed in more marked degree by the immune sera. In the case of haemolysis, it has not been possible to clearly demonstrate that the actions manifested by the normal and immune sera are distinct, although the weight of evidence is in favour of this view. In the case of ricin, however, it has been possible to demonstrate that the immune serum possesses properties which are quite distinct from those possessed by normal serum, and that the latter does not interfere with the action of ricin because of the natural presence of a trace of antiricin. In the case of immunity to ricin, the antitoxine is certainly something which has been super-added to the serum in consequence of the process of immunisation.The facts ascertained in regard to artificial immunity to erythrocytes and to ricin completely agree. Only in oue point is it impossible to be quite sure that the phenomena are identical, viz., in the simulation by normal serum of the powers characteristic of the immune serum; for the demonstration that the two are distinct has been possible for ricin, but open to doubt in the case of erythrocytes. My investigations have been extended to diphtheria and tetanus toxines and to cobra venom, kindly placed at my disposal by Sir Thomas R. Fraser. They have however been interrupted, but so far as they go they support fully the observations made on ricin and erythrocytes.


2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Ariane de Jesus Sousa-Batista ◽  
Wallace Pacienza-Lima ◽  
Natalia Arruda-Costa ◽  
Camila Alves Bandeira Falcão ◽  
Maria Ines Ré ◽  
...  

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.


2019 ◽  
Vol 11 (519) ◽  
pp. eaax4204 ◽  
Author(s):  
Camila Farias Amorim ◽  
Fernanda O. Novais ◽  
Ba T. Nguyen ◽  
Ana M. Misic ◽  
Lucas P. Carvalho ◽  
...  

Patients infected with Leishmania braziliensis develop chronic lesions that often fail to respond to treatment with antiparasite drugs. To determine whether genes whose expression is highly variable in lesions between patients might influence disease outcome, we obtained biopsies of lesions from patients before treatment with pentavalent antimony and performed transcriptomic profiling on these clinical samples. We identified genes that were highly variably expressed between patients, and the variable expression of these genes correlated with treatment outcome. Among the most variable genes in all the patients were components of the cytolytic pathway, and the expression of these genes correlated with parasite load in the skin. We demonstrated that treatment failure was linked to the cytolytic pathway activated during infection. Using a host-pathogen marker profile of as few as three genes, we showed that eventual treatment outcome could be predicted before the start of treatment in two separate cohorts of patients with cutaneous leishmaniasis (n = 21 and n = 25). These findings raise the possibility of point-of-care diagnostic screening to identify patients at high risk of treatment failure and provide a rationale for a precision medicine approach to drug selection in cutaneous leishmaniasis. This work more broadly demonstrates the value of identifying genes of high variability in other diseases to better understand and predict diverse clinical outcomes.


2014 ◽  
Vol 56 (4) ◽  
pp. 361-362 ◽  
Author(s):  
Erica de Camargo Ferreira e Vasconcellos ◽  
Maria Inês Fernandes Pimentel ◽  
Cláudia Maria Valete-Rosalino ◽  
Maria de Fátima Madeira ◽  
Armando de Oliveira Schubach

We report a case of a 42 year-old female, who came to a leishmaniasis reference center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in the right forearm. Treatment with low-dose intramuscular meglumine antimoniate (MA) (5 mg Sb5+/kg/day) was initiated, with improvement after 28 days, although with the development of generalized eczema. After 87 days, the lesion worsened. Patient refused treatment with amphotericin B. MA was then infiltrated in the lesion, in two sessions, resulting in local eczema, with bullae formation; however, twenty days after, both the ulcer and eczema receded. Intralesional administration of MA should be used carefully when previous cutaneous hypersensitivity is detected.


Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 891
Author(s):  
Aishah E. Albalawi ◽  
Sobhy Abdel-Shafy ◽  
Amal Khudair Khalaf ◽  
Abdullah D. Alanazi ◽  
Parastoo Baharvand ◽  
...  

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.


2021 ◽  
Vol 9 (6) ◽  
pp. 1147
Author(s):  
Aurora Diotallevi ◽  
Gloria Buffi ◽  
Giovanni Corbelli ◽  
Marcello Ceccarelli ◽  
Margherita Ortalli ◽  
...  

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.


2021 ◽  
Vol 2 (1) ◽  
pp. 54
Author(s):  
Anna Clara Silva Fonseca ◽  
Nathália Brígida de Oliveira ◽  
Daniela Camargos Costa

Introdução: A Leishmania braziliensis é um protozoário da família Trypanosomatidae responsável pelo desenvolvimento de uma das formas dermotrópicas da doença denominada leishmaniose mucosa (LM). O parasito é intracelular obrigatório e se multiplica dentro dos macrófagos e monócitos de seus hospedeiros. Os receptores tolllike (TLR) são glicoproteínas transmembrana presentes nas células de defesa, principalmente Natural Killer, macrófagos e células dendríticas, que reconhecem estruturas microbianas e que promovem uma série de sinais que produzem citocinas próinflamatórias importantes para que a resposta imune inata seja efetiva, como por exemplo TNF-α, IL-10 e TGF-β. Objetivo: Realizar revisão da literatura a respeito do papel dos receptores Toll-like na resposta à infecção in vitro por L. braziliensis. Material e métodos: Realizado no formato de revisão integrativa, a pesquisa abrangeu artigos científicos das bases de dados SCIELO e PUBMED. Os descritores utilizados foram “American Cutaneous leishmaniasis”, “Leishmania braziliensis”, “mucosal leishmaniasis” e “Toll-like receptors”. Foram selecionados artigos acadêmicos originais, escritos na língua inglesa, que foram publicados no período de 2014 a 2020, obtendo -se 20 artigos. Após a leitura dos títulos e resumos e ao adotar os critérios de exclusão, foram selecionados 12 artigos originais para a presente revisão. Resultados: As pesquisas selecionadas avaliaram 147 pacientes com diagnóstico histopatológico de Leishmaniose Cutânea (LC). Os pacientes que apresentavam LM, concomitantemente possuíam uma maior expressão de células TCD4+, TCD8+, IL-10+ e TGF-β+ em comparação com aqueles que possuíam LC, que expressavam uma menor quantidades dessas citocinas. Em oposição, o TNF-α em pacientes com LC, encontrava-se aumentado se comparada a LM. Na análise relacionada a TLR-2 e TLR-4, houve uma maior expressão em monócitos nos pacientes com LC associadas a L. braziliensis e que o bloqueio dos TRL reduziu as respostas oxidativas das células de pacientes com LC. Conclusão: Diante dos resultados é possível concluir que a maior expressão de TLR-2 e TLR-4 promove a hiper-reatividade de citocinas pró-inflamatórias e consequente pré-disposição para desenvolvimento da doença. Portanto, seu bloqueio é eficaz para redução das lesões. Esse dado demonstra a relação e o papel dos TLR na infecção por L. braziliensis, trazendo importantes esclarecimentos para a resposta imune e desenho vacinal.


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