Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.744
Filtrar
2.
Cochrane Database Syst Rev ; 8: CD004834, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853410

RESUMO

BACKGROUND: On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009. OBJECTIVES: To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML). SEARCH METHODS: We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome. MAIN RESULTS: We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.


Assuntos
Leishmaniose Cutânea/terapia , Administração Oral , Adulto , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Vacina BCG/uso terapêutico , Feminino , Humanos , Hipertermia Induzida , Imunocompetência , Injeções Intramusculares , Injeções Intravenosas , Interferon gama/uso terapêutico , Vacinas contra Leishmaniose/uso terapêutico , Leishmaniose Mucocutânea/terapia , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Pentoxifilina/administração & dosagem , Pentoxifilina/efeitos adversos , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Fosforilcolina/análogos & derivados , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
PLoS Negl Trop Dis ; 14(7): e0008429, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32687498

RESUMO

BACKGROUND: Few prospective data exist on incidence of post kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis (VL) relapse after different treatment regimens. METHODOLOGY/PRINCIPAL FINDINGS: A Phase IV trial included 1761 VL patients treated between 2012-2014 with single dose AmBisome (SDA; N = 891), miltefosine-paromomycin (Milt-PM; n = 512), or AmBisome-miltefosine (AmB-Milt; n = 358). Follow-up for PKDL and VL relapse was scheduled for 6, 12 and 24 months after treatment, lasting until 2017. Patients with lesions consistent with PKDL were tested by rK39 rapid test, and if positive, underwent skin-snip sampling, smear microscopy and PCR. Probable PKDL was defined by consistent lesions and positive rK39; confirmed PKDL required additional positive microscopy or PCR. PKDL and relapse incidence density were calculated by VL treatment and risk factors evaluated in Cox proportional hazards models. Among 1,750 patients who completed treatment, 79 had relapse and 104 PKDL. Relapse incidence density was 1.58, 2.08 and 0.40 per 1000 person-months for SDA, AmB-Milt and Milt-PM, respectively. PKDL incidence density was 1.29, 1.45 and 2.65 per 1000 person-months for SDA, AmB-Milt and Milt-PM. In multivariable models, patients treated with Milt-PM had lower relapse but higher PKDL incidence than those treated with SDA; AmB-Milt rates were not significantly different from those for SDA. Children <12 years were at higher risk for both outcomes; females had a higher risk of PKDL but not relapse. CONCLUSIONS/SIGNIFICANCE: Active surveillance for PKDL and relapse, followed by timely treatment, is essential to sustain the achievements of VL elimination programs in the Indian sub-continent.


Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Índia/epidemiologia , Leishmaniose Cutânea/patologia , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Adulto Jovem
4.
Int J Infect Dis ; 97: 204-207, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32505874

RESUMO

INTRODUCTION: Mucocutaneous leishmaniasis (MCL) is a complication of tegumentary leishmaniasis, causing potentially life-threatening lesions in the ear, nose, and throat (ENT) region, and most commonly due to Leishmania (Viannia) braziliensis. We report a case of relapsing MCL in an Italian traveler returning from Argentina. CASE DESCRIPTION: A 65-year-old Italian male patient with chronic kidney disease, arterial hypertension, prostatic hypertrophy, and type-2 diabetes mellitus was referred for severe relapsing MCL acquired in Argentina. ENT examination showed severe diffuse pharyngolaryngeal edema and erythema, partially obstructing the airways. A nasopharyngeal biopsy revealed a lymphoplasmacytic inflammation and presence of Leishmania amastigotes, subsequently identified as L. (V.) braziliensis by hsp70 PCR-RFLP analysis and sequencing. Despite receiving four courses of liposomal amphotericine B (L-AmB) and two courses of miltefosine over a 2-year period, the patient presented recurrence of symptoms a few months after the end of each course. After the patient was referred to us, a combined treatment was started with intravenous pentamidine 4 mg/kg on alternate days for 10 doses, followed by one dose per week for an additional seven doses, intralesional meglumine antimoniate on the nasal lesion once per week for six doses, oral azoles for three months, and aerosolized L-AmB on alternate days for three months. The treatment led to regression of mucosal lesions and respiratory symptoms. Renal function temporarily worsened, and the addition of insulin was required to maintain glycemic compensation after pentamidine discontinuation. CONCLUSIONS: This case highlights the difficulties in managing a life-threatening refractory case of MCL in an Italian traveler with multiple comorbidities. Even though parenteral antimonial derivatives are traditionally considered the treatment of choice for MCL, they are relatively contraindicated in cases of chronic kidney disease.The required dose adjustment in cases of impaired renal function is unknown, therefore the use of alternative drugs is recommended. This case was resolved with combination treatment, including aerosolized L-AmB, which had never been used before for MCL.


Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Azóis/administração & dosagem , Leishmaniose Mucocutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Pentamidina/administração & dosagem , Administração Intravenosa , Idoso , Argentina , Quimioterapia Combinada , Humanos , Leishmania braziliensis/efeitos dos fármacos , Leishmania braziliensis/fisiologia , Leishmaniose Mucocutânea/parasitologia , Masculino , Recidiva
5.
Rev Soc Bras Med Trop ; 53: e20200040, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578710

RESUMO

Mucocutaneous leishmaniasis (MCL) is a chronic infection that can affect the skin and mucous membranes. We report a case of oral, nasopharyngeal, and penile lesions in a 35-year-old cocaine user. The patient presented with ulcerated lesions in 2014. Histopathologic analysis revealed amastigotes, and serological test results were positive for leishmaniasis. Systemic therapy with meglumine antimoniate was administered; however, the patient failed to present for follow-up. In 2018, he returned with nasal collapse, and another histopathologic test confirmed MCL. This case illustrates the importance of careful differential diagnosis of skin and mucous ulcers to identify the particular pathology.


Assuntos
Antiprotozoários/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/complicações , Leishmaniose Mucocutânea/diagnóstico , Antimoniato de Meglumina/administração & dosagem , Adulto , Humanos , Leishmaniose Mucocutânea/complicações , Leishmaniose Mucocutânea/tratamento farmacológico , Masculino
6.
Am J Trop Med Hyg ; 103(1): 308-314, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32394874

RESUMO

Visceral leishmaniasis (VL) is endemic in Asia, East and North Africa, South America, and Southern Europe, and is a major public health problem in the Indian subcontinent. Miltefosine received approval in 2002 to treat VL in India, and the Indian National Vector Borne Disease Control Programme later adopted a single dose (10 mg/kg) of liposomal amphotericin B. We report results of a randomized trial comparing the efficacy of combination therapy with an Indian preparation of liposomal amphotericin B (single dose of 7.5 mg/kg) and short-course miltefosine (2.5 mg/kg/day for 14 days; n = 66) in comparison to miltefosine monotherapy (2.5 mg/kg/day for 28 days; n = 78). Nine patients in the miltefosine group and three in the combination therapy group had to discontinue therapy because of serious adverse events. At the end of the therapy, the clinical and parasitological cure rate was 100% in both groups. By per-protocol analysis, by 6 months after completion of treatment, 12 of 69 patients in the miltefosine monotherapy arm (17.4%, 95% CI: 10.24-28%) and none in the combination therapy arm had relapse. Over 5 years of follow-up, 10 patients in the miltefosine monotherapy arm (all within 0.5-2 years after completing therapy) and none in the combination therapy arm experienced post-kala-azar dermal leishmaniasis. Combination therapy offered benefits over miltefosine monotherapy for VL in India.


Assuntos
Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Adolescente , Adulto , Idoso , Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Criança , Quimioterapia Combinada , Feminino , Humanos , Índia , Leishmania donovani , Masculino , Pessoa de Meia-Idade , Fosforilcolina/administração & dosagem , Fosforilcolina/uso terapêutico , Adulto Jovem
7.
Am J Trop Med Hyg ; 103(3): 1076-1080, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32394886

RESUMO

Diffuse cutaneous leishmaniasis (DCL) is a rare type of leishmaniasis characterized by diffuse skin lesions. In Brazil, Leishmania (L.) amazonensis is the main etiological agent of this clinical form. The state of Maranhão has the highest prevalence of this disease in the country, as well as a high rate of HIV infection. Here, we report the first case of DCL/HIV of Brazil. A 46-year-old man from the Amazonian area of Maranhão state presented atypical lesion in the left upper limb and dissemination of diffuse erythematous nodules over his entire body. Histopathological examination confirmed the presence of intracellular amastigotes of Leishmania, and a polymerase chain reaction and molecular identification by restriction fragment profile identified L. (L.) amazonensis as the causative agent of the disease. The patient was also diagnosed with HIV virus after the leishmaniasis diagnosis. The initial treatments for leishmaniasis were liposomal amphotericin B (AmB-L) (4 mg/kg) for 10 days and prophylactic use of Glucantime® (10 mg/Sb+5/kg) for 2 months. After unsuccessful initial treatments, he was treated with a combination of AmB-L (4 mg/kg) alternated with pentamidine (4 mg/kg) for 10 days but failed in the first therapeutic cycle. Subsequently, he had a good response to treatment with pentamidine (4 mg/kg).


Assuntos
Antiprotozoários/administração & dosagem , Coinfecção , Infecções por HIV/diagnóstico , Leishmania/isolamento & purificação , Leishmaniose Tegumentar Difusa/diagnóstico , Antimoniato de Meglumina/administração & dosagem , Pentamidina/administração & dosagem , Anfotericina B/administração & dosagem , Infecções por HIV/virologia , Humanos , Leishmaniose Tegumentar Difusa/tratamento farmacológico , Leishmaniose Tegumentar Difusa/microbiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Intern Med ; 59(9): 1227-1230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378656

RESUMO

Liposomal-amphotericin B (L-AmB) is used for cutaneous leishmaniasis (CL); however, its treatment failure has not yet been described in detail. A 58-year-old man returned from the Republic of Venezuela with a cutaneous ulcer on his left lower leg. The causative pathogen was Leishmania braziliensis. We started L-AmB 3 mg/kg/day for 6 days; however, the ulcer did not resolve. The patient was successfully retreated with a higher dose L-AmB 4 mg/kg/day 9 times (total, 36 mg/kg). If L-AmB fails to treat CL and other therapeutics cannot be used, increasing the L-AmB dose is a viable option.


Assuntos
Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Diagnóstico Diferencial , Relação Dose-Resposta a Droga , Humanos , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Retratamento , Falha de Tratamento
9.
Poult Sci ; 99(4): 1983-1987, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241480

RESUMO

Histomoniasis is currently a re-emerging disease of major significance for many commercial turkey and broiler breeder production companies because of the unavailability of drugs or vaccines. The protozoa Histomonas meleagridis (HM) requires the presence of enteric microflora to promote the disease. The objectives of this research note were to evaluate the effect of dietary administration of sodium chlorate (SC) and sodium nitrate (SN) in vitro and in vivo for HM prophylaxis in poults. A total of 128 day-of-hatch female poults obtained from a commercial hatchery were wing-tagged and randomly assigned into 1 of 4 experimental groups: negative control (NC), positive control, dietary inclusion of SC (3,200 ppm) and SN (500 ppm). Poults from groups SC and SN started on their respective diets on day 12. All groups, except the NC, were challenged with 2 × 105 HM on day 19. Controls were fed a basal diet, identical to the treatment diets but not supplemented with SC or SN. Body weight gain (BWG) was determined weekly, starting on day 1 until day 28, and postchallenge morbidity and mortality were recorded. On day 28 of age, all surviving poults were lesion scored for hepatic and cecal lesions. Ceca and distal ileum were collected on day 28 for bacterial recovery on selective media for total aerobic, lactic acid bacteria, or gram-negative bacteria. The addition of SC and SN in the in vitro growth of HM greatly reduced the growth of the protozoa after 20 h of incubation when compared with the control nontreated group (P < 0.05). However, dietary supplementation of SC and SN had no effect against HM in vivo, as was demonstrated by BWG, the severity of lesions in the liver and ceca or bacterial recovery of treated poults when compared with the positive control group.


Assuntos
Antibioticoprofilaxia/veterinária , Antiprotozoários/metabolismo , Cloratos/metabolismo , Nitratos/metabolismo , Doenças das Aves Domésticas/prevenção & controle , Infecções Protozoárias em Animais/prevenção & controle , Perus , Ração Animal/análise , Animais , Antiprotozoários/administração & dosagem , Cloratos/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Nitratos/administração & dosagem , Doenças das Aves Domésticas/parasitologia , Infecções Protozoárias em Animais/parasitologia , Trichomonadida/efeitos dos fármacos
10.
Am J Trop Med Hyg ; 103(3): 1081-1084, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32314693

RESUMO

We present two cases of Leishmania (V) panamensis in returning travelers from Central America successfully treated with miltefosine. The couple presented with ulcerative skin lesions nonresponsive to antibiotics. Skin biopsy with polymerase chain reaction (PCR) revealed L. (V) panamensis. To prevent the development of mucosal disease and avoid the inconvenience of parental therapy, we treated both patients with oral miltefosine. We suggest that miltefosine represents an important therapeutic alternative in the treatment of cutaneous lesions caused by L. panamensis and in preventing mucosal involvement.


Assuntos
Antiprotozoários/administração & dosagem , Leishmania guyanensis/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Fosforilcolina/análogos & derivados , Administração Oral , Adulto , Biópsia , América Central , Feminino , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Masculino , Fosforilcolina/administração & dosagem , Reação em Cadeia da Polimerase , Pele/parasitologia , Viagem
11.
PLoS Negl Trop Dis ; 14(3): e0008125, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214337

RESUMO

BACKGROUND: The disturbance of host metabolic pathways by Leishmania parasites has crucial consequences for the activation status of immune cells and the outcome of infection. Glutamine has been described as an immunomodulatory amino acid, yet its role during Leishmania infection is still unknown. METHODS: We performed transcriptomics in uninfected and L. donovani-infected macrophages 6 hours post-infection. Glutamine quantification by HPLC was assessed in the supernatant of macrophages throughout the infection course. For experimental L. donovani infections, mice were infected with 1.0 x 108 stationary L. donovani promastigotes. Glutaminase (GLS) chemical inhibition was performed using BPTES and glutamine was administered throughout infection. For combined therapy experiment, a daily administration of miltefosine and glutamine was performed by oral gavage. Parasite burden was determined using a Taqman-based assay. Immune cell phenotyping and cytotoxicity were performed in splenic cells using flow cytometry. FINDINGS: We show that glutamine is essential for the control of L. donovani infection. Transcriptomic analysis of L. donovani-infected macrophages demonstrated an upregulation of genes involved in glutamine metabolism. Pharmacological inhibition of glutaminolysis significantly increased the susceptibility to infection, accompanied by an increased recruitment of anti-inflammatory myeloid cells and impaired T cell responses. Remarkably, the supplementation of glutamine to mice infected with L. donovani during miltefosine treatment potentiates parasite clearance through the development of a more effective anti-Leishmania adaptive immune response. CONCLUSIONS: Our data indicates that dietary glutamine supplementation may act as a promising adjuvant for the treatment of visceral leishmaniasis.


Assuntos
Antiprotozoários/administração & dosagem , Suplementos Nutricionais , Glutamina/administração & dosagem , Fatores Imunológicos/administração & dosagem , Leishmaniose Visceral/terapia , Fosforilcolina/análogos & derivados , Animais , Modelos Animais de Doenças , Feminino , Humanos , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos C57BL , Carga Parasitária , Fosforilcolina/administração & dosagem , Subpopulações de Linfócitos T/imunologia , Resultado do Tratamento
12.
Molecules ; 25(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204358

RESUMO

Leishmaniasis affects around 12 million people worldwide and is estimated to cause the ninth-largest disease burden. There are three main forms of the disease, visceral (VL), cutaneous (CL), and mucocutaneous (MCL), leading to more than one million new cases every year and several thousand deaths. Current treatments based on chemically synthesized molecules are far from ideal. In this study, we have tested the in vitro and in vivo efficacy of ursolic acid (UA), a multifunctional triterpenoid with well-known antitumoral, antioxidant, and antimicrobial effects on different Leishmania strains. The in vitro antileishmanial activity against the intracellular forms was six and three-fold higher compared to extracellular forms of L. amazonensis and L. infantum, respectively. UA also showed to be a potent antileishmanial drug against both VL and CL manifestations of the disease in experimental models. UA parenterally administered at 5 mg/kg for seven days significantly reduced the parasite burden in liver and spleen not only in murine acute infection but also in a chronic-infection model against L. infantum. In addition, UA ointment (0.2%) topically administered for four weeks diminished (50%) lesion size progression in a chronic infection model of CL caused by L. amazonensis, which was much greater than the effect of UA formulated as an O/W emulsion. UA played a key role in the immunological response modulating the Th1 response. The exposure of Leishmania-infected macrophages to UA led to a significant different production in the cytokine levels depending on the Leishmania strain causing the infection. In conclusion, UA can be a promising therapy against both CL and VL.


Assuntos
Antiprotozoários/administração & dosagem , Leishmania infantum/efeitos dos fármacos , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Triterpenos/administração & dosagem , Administração Tópica , Animais , Antiprotozoários/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Infusões Parenterais , Leishmaniose Visceral/parasitologia , Fígado/efeitos dos fármacos , Fígado/parasitologia , Masculino , Mesocricetus , Camundongos , Phytolaccaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Baço/efeitos dos fármacos , Baço/parasitologia , Triterpenos/farmacologia
14.
Pediatr Infect Dis J ; 39(3): 254-255, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32032311

RESUMO

We describe the case of a 7-year-old girl with repeated vaginal Enterobius vermicularis infection, never detected as a digestive tract infection. Two-dose pyrantel pamoate or 2-dose albendazole could not suppress recurrence. Finally, 3-dose albendazole after 2-week intervals was successful in preventing relapse.


Assuntos
Albendazol/uso terapêutico , Antiprotozoários/uso terapêutico , Enterobius/efeitos dos fármacos , Oxiuríase/tratamento farmacológico , Oxiuríase/parasitologia , Vaginite/tratamento farmacológico , Vaginite/parasitologia , Albendazol/administração & dosagem , Animais , Antiprotozoários/administração & dosagem , Criança , Esquema de Medicação , Feminino , Humanos , Oxiuríase/transmissão , Recidiva , Resultado do Tratamento
15.
Eur J Pharm Sci ; 145: 105256, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32032778

RESUMO

The present study evaluates the efficacy of sodium stibogluconate (SSG) co-loaded with ketoconazole (KTZ) in nano-elastic liposomes (NELs) for the topical treatment of cutaneous leishmaniasis (CL). SSG-KTZ co-loaded NELs were developed and assessed for various physicochemical properties and anti-leishmanial potential. The optimized nano-vesicles have an average size of 212.8 ± 3.1 nm and entrapment efficiency of 61.2 ± 2.9%. SSG-KTZ co-loaded NELs displayed 5.37-fold higher skin permeation of SSG as compared to drug solution. SSG and KTZ displayed a synergistic interaction and flow cytometry revealed enhanced killing of DsRed Leishmania mexicana in infected macrophages. In-vitro and in-vivo anti-leishmanial studies indicated a 10.67-fold lower IC50 value and a 35.33-fold reduced parasitic burden as compared with plain SSG solution, respectively. SSG-KTZ co-loaded NELs were found to be a promising approach for the topical treatment of CL.


Assuntos
Gluconato de Antimônio e Sódio/administração & dosagem , Antiprotozoários/administração & dosagem , Elasticidade , Cetoconazol/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Nanopartículas/administração & dosagem , Administração Tópica , Animais , Gluconato de Antimônio e Sódio/metabolismo , Antiprotozoários/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Feminino , Cetoconazol/metabolismo , Leishmaniose Cutânea/metabolismo , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/metabolismo , Técnicas de Cultura de Órgãos , Distribuição Aleatória , Pele/efeitos dos fármacos , Pele/metabolismo
16.
PLoS One ; 15(2): e0228996, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053698

RESUMO

BACKGROUND: The plenteous resistance to and undesirable consequences of the existing antipiroplasmic therapies have emphasized the urgent need for new chemotherapeutics and drug targets for both prophylaxis and chemotherapy. Hydroxyurea (HYD) is an antineoplastic agent with antitrypanosomal activity. Eflornithine (α-difluoro-methyl ornithine, DFMO) is the best choice therapy for the treatment of late-stage Gambian human African trypanosomiasis. METHODS: In this study, the inhibitory and combination efficacy of HYD and DFMO with existing babesicidal drugs (diminazene aceturate (DA), atovaquone (ATV), and clofazimine (CLF)) deoxyribonucleotide in vitro against the multiplication of Babesia and Theileria. As well as, their chemotherapeutic effects were assessed on B. microti strain that infects rodents. The Cell Counting Kits-8 (CCK-8) test was used to examine their cytotoxicity on human foreskin fibroblast (HFF), mouse embryonic fibroblast (NIH/3T3), and Madin-Darby bovine kidney (MDBK) cells. FINDINGS: HYD and DFMO suppressed the multiplication of all tested species (B. bigemina, B. bovis, B. caballi, B. divergens, and T. equi) in a dose-related manner. HFF, NIH/3T3, or MDBK cell viability was not influenced by DFMO at 1000 µM, while HYD affected the MDBK cell viability at EC50 value of 887.5±14.4 µM. The in vitro combination treatments of DFMO and HYD with CLF, DA, and ATV exhibited synergistic and additive efficacy toward all tested species. The in vivo experiment revealed that HYD and DFMO oral administration at 100 and 50 mg/kg inhibited B. microti multiplication in mice by 60.1% and 78.2%, respectively. HYD-DA and DFMO-DA combined treatments showed higher chemotherapeutic efficacy than their monotherapies. CONCLUSION: These results indicate the prospects of HYD and DFMO as drug candidates for piroplasmosis treatment, when combined mainly with DA, ATV, and CLF. Therefore, further studies are needed to combine HYD or DFMO with either ATV or CLF and examine their impact on B. microti infection in mice.


Assuntos
Babesia/efeitos dos fármacos , Eflornitina/efeitos adversos , Eflornitina/farmacologia , Hidroxiureia/efeitos adversos , Hidroxiureia/farmacologia , Theileria/efeitos dos fármacos , Animais , Antineoplásicos , Antiprotozoários/administração & dosagem , Antiprotozoários/farmacologia , Atovaquona/efeitos adversos , Atovaquona/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Clofazimina/efeitos adversos , Clofazimina/farmacologia , Diminazena/efeitos adversos , Diminazena/análogos & derivados , Diminazena/farmacologia , Cães , Prepúcio do Pênis/citologia , Humanos , Masculino , Camundongos , Células NIH 3T3
17.
Int J Pharm ; 578: 119057, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31991188

RESUMO

Miltefosine (MF), an alkylphospholipid originally developed for breast cancer treatment, is a highly active drug for the treatment against leishmaniasis, a neglected tropical disease considered the world's second leading cause of death by a parasitic agent after malaria. MF exhibits dose-limiting gastrointestinal side effects in patients and its penetration through lipophilic barriers is reduced. In this work we propose a reformulation of MF by incorporating the drug to poly(ethylene)oxide (PEO)-based polymeric micelles, specifically, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Tetronic block copolymers (T904 and T1107). A full structural characterization of the aggregates has been carried out by SANS (small-angle neutron scattering) and dynamic light scattering (DLS), in combination with proton 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, to determine the precise location of the drug. The structure of MF micelles has been characterized as a function of the temperature and concentration. In the presence of the block-copolymers, MF forms mixed micelles in a wide range of temperatures, TPGS being the co-surfactant that incorporates more MF unimers. The hydrophobic tail of MF and those of the block copolymers are in close contact within the micelles, which present a core-shell structure with a hydrophilic corona formed by the PEG blocks of the TPGS and the zwitterion head group of the MF. In order to identify the best carrier, the antileishmanicidal activity of MF in the different formulations has been tested on macrophages, promastigotes and intracellular amastigotes. The combination of the three vehicles with MF makes the formulated drug more active than MF alone against L. major promastigotes, however, only the combination with T904 increases the MF activity against intracellular amastigotes. With the aim of exploring gel-based formulations of the drug, the combination of MF and T1107 under gelation conditions has also been investigated.


Assuntos
Antiprotozoários/administração & dosagem , Portadores de Fármacos/administração & dosagem , Etilenodiaminas/administração & dosagem , Leishmania major/efeitos dos fármacos , Micelas , Fosforilcolina/análogos & derivados , Vitamina E/administração & dosagem , Animais , Antiprotozoários/química , Portadores de Fármacos/química , Difusão Dinâmica da Luz , Etilenodiaminas/química , Macrófagos/parasitologia , Camundongos , Estrutura Molecular , Nanopartículas/administração & dosagem , Nanopartículas/química , Fosforilcolina/administração & dosagem , Fosforilcolina/química , Análise Espectral , Vitamina E/química
18.
Carbohydr Polym ; 232: 115826, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952620

RESUMO

The study investigated chitosan coated nanostructured lipid carriers (NLCs) for oral delivery of albendazole in treatment of trichinellosis. NLCs comprised precirol and oleic acid with Tween and Span 80. Dicetylphosphate was used as charging agent to allow chitosan coating. Trichinella spiralis infected mice were used and albendazole suspension, coated or uncoated NLCs were orally administered at different stages of infection. NLCs were spherical with size of 188 and 200 nm for coated and uncoated NLC, respectively. Treatment during intestinal phase reduced worm count with NLCs showing better rank. This was reflected further by reduced larvae count and improved histopathological features. Starting treatment in the migrating phase reduced larval count by 62.9, 99.6 and 89.5 % after administration of suspension, coated and uncoated NLCs, respectively. The same rank was recorded for the encysted phase. NLCs enhanced the efficacy of albendazole against Trichinella spiralis compared with suspension with chitosan coated NLCs being superior.


Assuntos
Albendazol/farmacologia , Antiprotozoários/farmacologia , Quitosana/química , Lipídeos/química , Nanoestruturas/química , Trichinella spiralis/efeitos dos fármacos , Administração Oral , Albendazol/administração & dosagem , Albendazol/química , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/química , Quitosana/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Lipídeos/administração & dosagem , Nanoestruturas/administração & dosagem , Testes de Sensibilidade Parasitária , Tamanho da Partícula , Propriedades de Superfície
19.
Diagnosis (Berl) ; 7(1): 69-73, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31256063

RESUMO

Background Liver abscess is the most common extraintestinal manifestation of Entamoeba histolytica. Clinical manifestations could appear after returning from an endemic area or several years after the exposure. The diagnosis usually requires microbiological confirmation. Case presentation We present a case of a 55-year-old woman diagnosed with Crohn's disease treated with immunosuppressive drugs, who was admitted to the Emergency Service with liver parenchyma abscesses. Computed tomography (CT)-guided puncture showed pus, and both Gram staining and fresh parasite visualization were negative. Hepatic pus bacteriological culture was reported as negative and parasite multiplex polymerase chain reaction (PCR) was performed, being positive for E. histolytica. The same PCR was performed on blood, pleural fluid and stool samples, all of them being positive for E. histolytica. Conclusions Reviewing the clinical history of this patient, it was observed that parasite detection in three stool samples was negative 2 months before the current admission. Due to the lack of sensitivity of the microscopy techniques, we propose to routinely perform parasite detection in stools using molecular techniques, especially in immunocompromised patients.


Assuntos
Entamoeba histolytica/genética , Fezes/parasitologia , Abscesso Hepático/parasitologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Cefotaxima/administração & dosagem , Cefotaxima/uso terapêutico , Feminino , Humanos , Hospedeiro Imunocomprometido , Enteropatias Parasitárias/complicações , Abscesso Hepático/diagnóstico por imagem , Abscesso Hepático/terapia , Metronidazol/administração & dosagem , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Reação em Cadeia da Polimerase/métodos , Punções/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
20.
Drug Deliv Transl Res ; 10(2): 403-412, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31701487

RESUMO

Leishmaniasis occurs in the five continents and represents a serious public health challenge, but is still a neglected disease, and the current pharmacological weaponry is far from satisfactory. Triglyceride-rich nanoparticles mimicking chylomicrons (TGNP) behave metabolically like native chylomicrons when injected into the bloodstream. Previously we have shown that TGNP as vehicle to amphothericin B (AB) for treatment of fungi infection showed reduced renal toxicity and lower animal death rates compared to conventional AB. The aim of the current study was to test the tolerability and effectiveness of the TGNP-AB preparation in a murine model of Leishmania amazonensis infection. The in vitro assays determined the cytotoxicity of TGNP-AB, AB, and TGNP in macrophages and promastigote forms and the leishmanicidal activity in infected macrophages. The in vivo toxicity tests were performed in healthy mice with increasing doses of TGPN-AB and AB. Then, animals were treated with 2.5 mg/kg/day of AB, 17.5 mg/kg/day of TGNP-AB, or TGNP three times a week for 4 weeks. TGNP-AB formulation was less cytotoxic for macrophages than AB. TGNP-AB was more effective than AB against the promastigotes forms of the parasite and more effective in reducing the number of infected macrophages and the number of amastigotes forms per cell. TGNP-AB-treated animals showed lower hepatotoxicity. In addition, TGNP-AB group showed a marked reduction in lesion size on the paws and parasitic load. The TGNP-AB preparation attained excellent leishmanicidal activity with remarkable lower drug toxicity at very high doses that, due to the toxicity-buffering properties of the nanocarrier, become fully tolerable.


Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Quilomícrons/química , Leishmaniose Cutânea/tratamento farmacológico , Triglicerídeos/química , Anfotericina B/química , Anfotericina B/farmacologia , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Composição de Medicamentos , Feminino , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Mimetismo Molecular , Nanopartículas , Carga Parasitária
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA