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1.
Am J Trop Med Hyg ; 102(2): 268-273, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31872796

RESUMO

In immunocompromised patients, visceral leishmaniasis (VL) can present with atypical clinical symptoms that include poor response to treatment. No optimal therapeutic regimen is available for such cases. In a splenectomized male patient, we observed a disseminated form of the disease in the liver, bone marrow, lymph nodes, and gastrointestinal tract. There was an apparent clinical improvement when he was initially treated with liposomal amphotericin B (L-AmB), but this was followed by a relapse involving severe clinical symptoms. He was finally treated successfully with a combination of L-AmB, meglumine antimoniate, and pentamidine isethionate. It is important to include asplenia as an immunosuppressive condition that induces exotic VL pathologies. In such cases, combination anti-Leishmania drug therapy should be considered.


Assuntos
Anfotericina B/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Pentamidina/uso terapêutico , Esplenectomia , Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Medula Óssea/parasitologia , Quimioterapia Combinada , Humanos , Hospedeiro Imunocomprometido , Mucosa Intestinal/parasitologia , Leishmaniose Visceral/imunologia , Linfonodos/parasitologia , Masculino , Antimoniato de Meglumina/administração & dosagem , Pessoa de Meia-Idade , Pentamidina/administração & dosagem
2.
BMJ Case Rep ; 12(12)2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31848140

RESUMO

Visceral leishmaniasis (VL) is a protozoan infection caused by Leishmania infantum and L. donovani with a higher incidence and severity in HIV-infected patients due to its synergistic effect on hampering the immune response, often leading to death after treatment failure. Literature regarding the management of relapsing VL in HIV-coinfected patients is lacking. Many experts recommend a combined therapy with liposomal amphotericin B and miltefosine. The use of pentavalent antimonials is often discouraged due to their toxicity. We report two cases of successful response to treatment with combined therapy with meglumine antimoniate followed by secondary prophylaxis with miltefosine and atovaquone on relapsing VL in two HIV-coinfected patients despite treatment and monthly prophylaxis with appropriate doses of liposomal amphotericin B.


Assuntos
Atovaquona/uso terapêutico , Infecções por HIV/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Adulto , Anfotericina B/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Prevenção Secundária , Resultado do Tratamento
3.
PLoS Negl Trop Dis ; 13(11): e0007788, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31693661

RESUMO

INTRODUCTION: Cutaneous leishmaniasis (CL), endemic in Bolivia, mostly affects poor people in rainforest areas. The current first-line treatment consists of systemic pentavalent antimonials (SPA) for 20 days and is paid for by the Ministry of Health (MoH). Long periods of drug shortages and a lack of safe conditions to deliver treatment are challenges to implementation. Intralesional pentavalent antimonials (ILPA) are an alternative to SPA. This study aims to compare the cost of ILPA and SPA, and to estimate the health and economic impacts of changing the first-line treatment for CL in a Bolivian endemic area. METHODS: The cost-per-patient treated was estimated for SPA and ILPA from the perspectives of the MoH and society. The quantity and unit costs of medications, staff time, transportation and loss of production were obtained through a health facility survey (N = 12), official documents and key informants. A one-way sensitivity analysis was conducted on key parameters to evaluate the robustness of the results. The annual number of patients treated and the budget impact of switching to ILPA as the first-line treatment were estimated under different scenarios of increasing treatment utilization. Costs were reported in 2017 international dollars (1 INT$ = 3.10 BOB). RESULTS: Treating CL using ILPA was associated with a cost-saving of $248 per-patient-treated from the MoH perspective, and $688 per-patient-treated from the societal perspective. Switching first-line treatment to ILPA while maintaining the current budget would allow two-and-a-half times the current number of patients to be treated. ILPA remained cost-saving compared to SPA in the sensitivity analysis. CONCLUSIONS: The results of this study support a shift to ILPA as the first-line treatment for CL in Bolivia and possibly in other South American countries.


Assuntos
Antiprotozoários/economia , Orçamentos , Redução de Custos , Leishmaniose Cutânea/tratamento farmacológico , Gluconato de Antimônio e Sódio/economia , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Bolívia , Análise Custo-Benefício , Custos de Medicamentos , Custos de Cuidados de Saúde , Humanos , Antimoniato de Meglumina/economia , Antimoniato de Meglumina/uso terapêutico
4.
Vet Parasitol ; 276: 108976, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31739256

RESUMO

Cutaneous leishmaniosis (CL) is a parasitic disease in animals and human with no satisfactory treatments and vaccination. Rapamycin is a potent inhibitor of mammalian target of rapamycin (mTOR) with various applications. Here, the effect of rapamycin alone or in combination with two other drugs, namely amphotericin B (AmB) and glucantime, was investigated against Leishmania tropica infection. In vitro viability and electron microscopy evaluation of the parasites showed detrimental changes in their appearance and viability. Treatment with clinically relevant dose of rapamycin (10.2 µg/dose) is able to control the parasite load in BALB/c mice infected with L. tropica. Furthermore, the cytokine profiles showed significant polarization towards Th1 immune response. Surprisingly, combination therapy with either AmB or glucantime was not efficient. Rapamycin is showed an effective alternative therapy against leishmaniosis caused by L. tropica.


Assuntos
Antiprotozoários/uso terapêutico , Leishmania tropica/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Sirolimo/uso terapêutico , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Animais , Antiprotozoários/farmacologia , Linhagem Celular Tumoral , Citocinas/análise , Feminino , Humanos , Concentração Inibidora 50 , Leishmania tropica/crescimento & desenvolvimento , Leishmania tropica/ultraestrutura , Leishmaniose Cutânea/prevenção & controle , Linfonodos/parasitologia , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Carga Parasitária , Distribuição Aleatória , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/efeitos dos fármacos
5.
Res Vet Sci ; 126: 131-138, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491669

RESUMO

This study examines correlations among serum proteins, clinical score, body weight and kidney function biomarkers after a standard treatment course (meglumine antimoniate plus allopurinol) in twelve Canine leishmaniosis (CanL) patients at the three times points pre treatment, after treatment and after the end of treatment. The laboratory variables measured were those used for the follow-up of sick dogs along with biomarkers of kidney function: glomerular filtration rate (GFR), creatinine (Cr), urea, calcium, inorganic phosphorus, urine specific gravity (USG) and urine protein to creatinine ratio (UPC). Arterial blood pressure (systolic blood pressure, SBP), clinical score (CS) and weight were also monitored over the study period. At Tp0, GFR was within the normal range in most dogs. Hyperfiltration was detected in three patients and hypofiltration in one. In dogs showing hyperfiltration, this factor remained in the non-azotemic range over the whole study period. After treatment normal filtration values were recovered. Meglumine antimoniate did not modify GFR or USG. A significant reduction in UPC was recorded. In all dogs, clinical scores improved. Negative correlation was found between GFR and Cr, UPC and albumin (Alb) and CS and Alb, while positive correlation was detected between UPC and total globulins (GlobT), CS and GlobT, UPC and total solids (TS), SBP and CS and SBP and UPC. Our findings indicate no impacts on kidney function of the treatment of CanL with meglumine antimoniate, as no effects were produced on GFR or USG. Treatment was effective and found to reduce UPC which could suggest improved glomerular injury.


Assuntos
Antiprotozoários/uso terapêutico , Doenças do Cão/tratamento farmacológico , Nefropatias/veterinária , Leishmaniose Visceral/veterinária , Antimoniato de Meglumina/uso terapêutico , Alopurinol/administração & dosagem , Animais , Antiprotozoários/efeitos adversos , Biomarcadores , Creatinina/urina , Cães , Feminino , Taxa de Filtração Glomerular , Nefropatias/induzido quimicamente , Leishmania infantum , Leishmaniose Visceral/tratamento farmacológico , Masculino , Antimoniato de Meglumina/administração & dosagem
6.
Exp Parasitol ; 206: 107768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539540

RESUMO

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.


Assuntos
Alopurinol/efeitos adversos , Doenças do Cão/tratamento farmacológico , Audição/efeitos dos fármacos , Rim/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Paromomicina/efeitos adversos , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Animais , Cóclea/efeitos dos fármacos , Creatinina/sangue , Doenças do Cão/parasitologia , Cães , Método Duplo-Cego , Combinação de Medicamentos , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/induzido quimicamente , Perda Auditiva/veterinária , Injeções Subcutâneas/veterinária , Leishmania infantum , Leishmaniose Visceral/tratamento farmacológico , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Antimoniato de Meglumina/uso terapêutico , Exame Neurológico/veterinária , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Distribuição Aleatória , Vestíbulo do Labirinto/efeitos dos fármacos
7.
Farm. comunitarios (Internet) ; 11(3): 13-18, sept. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-186879

RESUMO

Antecedentes: la leishmaniosis es una zoonosis vectorial que en humanos inmunodeprimidos presenta forma sistémica, estando la forma cutánea infradiagnosticada. El tratamiento para el portador tiene un elevado coste. Propietarios y centros de adopciones carecen de recursos, pero no tratar o prevenir implica tener a un portador de una zoonosis disponible para el vector. Por ello existe una tendencia a la sustitución por la presentación de humana por los agentes implicados, adelantándose a los responsables en materia de salud pública. Objetivos: conocer la incidencia de animales portadores, la proporción de medicamentos prescritos por los veterinarios, las tendencias de búsqueda en internet de medicamentos para prevención y el tratamiento. Metodología: análisis serológico por técnica de inmunoensayo de 255 perros, aplicación de precios de mercado a los resultados, encuesta sobre la prescripción de veterinarios clínicos y análisis de tendencias de búsqueda de información en internet entre usuarios. Resultados: 38 perros resultaron ser portadores inaparentes (infectados, pero no enfermos) y 28 portadores enfermos. El resto son no portadores. Se obtuvo una diferencia de precio de más del 50 % en el tratamiento entre medicamentos de humana o genéricos y el de veterinaria. En la prevención la diferencia es 11 veces el precio veterinario frente al de humana. Los veterinarios prescriben correctamente, pero informan de otras opciones más baratas y la tendencia de búsqueda en internet está orientada al precio y a la sustitución. Conclusión: el precio es la principal causa de sustitución del medicamento prescrito y la legislación no está atendiendo la relevancia de esta zoonosis. Las autoridades sanitarias han de valorar las necesidades reales en materia de salud pública


Background: Leishmaniasis is a vectorial zoonosis with systemic presentation in immunosuppressed humans, the cutaneous form is underdiagnosed. A lot of owners and Rescue kennels can not pay the treatment because it is very expensive, but not treating or not preventing is dangerous for Public Health. Therefore, there is a tendency to replace the veterinary drug by the human drug form, ahead of those responsible for Public Health. Objectives: To know the disease carrier animals, the prescription tendencies of the veterinarians, the tendencies of search in Internet of drugs for prevention and treatment. Methods: Blood test of 255 animals, application of market prices to the results, survey on the prescription of clinical veterinarians and analysis of Internet search trends among users. Results: 38 dogs were founded inapparent carriers (infected, but not ill) and 28 sick carriers. The rest were non-carriers. A price difference of more than 50 % was obtained in the treatment between human or generic drugs and that of veterinary medicine. About the prevention, the difference is 11 times the veterinary price compared to that of humans. Veterinarians prescribe correctly but report other cheaper options and the search trend on the internet is price and replacement oriented. Conclusion: The price is the main cause of substitution and the legislation is not agree the relevance of this zoonosis. The health authorities must assess the real needs in terms of Public Health


Assuntos
Animais , Cães , Leishmania/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Leishmaniose/veterinária , Farmácias , Substituição de Medicamentos/tendências , Drogas Veterinárias , Meglumina/uso terapêutico , Antimoniato de Meglumina/uso terapêutico , Antiprotozoários
8.
Georgian Med News ; (291): 122-125, 2019 Jun.
Artigo em Russo | MEDLINE | ID: mdl-31418744

RESUMO

In this study, we studied the activity of the antibacterial drugDoxycycline (Russia), and the control was the drug of pentavalent antimony - Glucantim (France), which for a long time was the "gold standard" in the treatment of any form of leishmaniasis. In the course of the experiment, the leading positions of doxycycline established in vitro. Its minimum doses lead to absolute suppression of the mobility of the pathogen L. major. Increasing the therapeutic dose of the drug is not justified. Comparison of this drug with the gold standard of therapy with meglumine antimonate (glucantim) showed its superiority in all indicators.


Assuntos
Doxiciclina/uso terapêutico , Leishmaniose/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Humanos , Técnicas In Vitro
9.
Exp Parasitol ; 205: 107747, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442454

RESUMO

Development of new chemotherapeutic agents is an essential issue in the treatment and control of a disease. This study aimed to evaluate the anti-leishmanial activity of amiodarone, an antiarrhythmic class III drug, against Leishmania major, the most prevalent etiological agent of cutaneous leishmaniasis in the old world. The proliferation of promastigotes and intracellular amastigotes in the absence or presence of amiodarone was estimated, in an in vitro study. For in vivo study, five weeks after infection of BALB/c mice with L. major, when the lesions appeared at the injection site, the mice were divided into four groups (n = 6 each); treatment was conducted for 28 consecutive days with vehicle, amiodarone at 40 mg/kg orally and glucantime at 60 mg/kg intraperitoneally. Therapy with amiodarone reduced the size of lesions compared to the untreated group after 12 days. Amiodarone decreased the parasite load and inflammatory responses, particularly the macrophages containing amastigotes, and enhanced granulation tissue formation in the dermis and subcutaneous area. The Tumor necrosis factor-α and Interleukin-6 levels were significantly lower in the cell culture supernatants of the inguinal lymph node in the amiodarone treated group compared to the vehicle and untreated groups. Amiodarone significantly increased the activity of glutathione peroxidase in comparison to the vehicle and untreated groups but did not affect the plasma levels of superoxide dismutase, malondialdehyde, adiponectin, and ferric reducing ability of plasma. Therefore, the anti- L. major activity and immunomodulatory effects of amiodarone reduced the parasitic load and enhanced wound healing in cutaneous leishmaniasis in BALB/c mice. Amiodarone reduced the lesion surface area, but it did not cure it completely.


Assuntos
Amiodarona/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Adiponectina/sangue , Amiodarona/farmacologia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiprotozoários/farmacologia , Linhagem Celular , Feminino , Glutationa Peroxidase/metabolismo , Concentração Inibidora 50 , Interleucina-6/análise , Leishmania major/ultraestrutura , Leishmaniose Cutânea/parasitologia , Linfonodos/química , Linfonodos/imunologia , Macrófagos/parasitologia , Malondialdeído/sangue , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Distribuição Aleatória , Pele/parasitologia , Pele/patologia , Pele/ultraestrutura , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/análise
10.
Turkiye Parazitol Derg ; 43(2): 55-59, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31204455

RESUMO

Objective: Cutaneous leishmaniasis (CL) is one of the common parasitic diseases in tropical and subtropical areas and is one of the important health problems in Iran. In order to investigate epidemiological aspects of CL disease in city of Aran va Bidgol in Isfahan province, this study was carried out in this central region of Iran. Methods: This cross-sectional study was conducted in over a period of eight years between 2009-2016. Direct smears were prepared from all patients and were examined by a light microscopy. The basic demographic and clinical data of patients with CL disease referred to health care centers were collected and then were analyzed by using the SPSS software. Results: Overall, 926 patients, including 542 (58.5%) males and 384 (41.5%) females with confirmed CL were identified. The CL disease was more common among males (58.5%). The highest and lowest incidence of the CL disease were estimated as 238.5 and 44.2 per 100000 people in 2009 and 2016, respectively. The highest incidence of the CL disease (26.3%) was observed in the age group of 0-9 years. Most of the cases (54%) were seen in autumn. More lesions (44.7%) were seen on the hands. Of the patients, 65.4% were treated by systemic glucantime regimen. Conclusion: According to the results of this investigation, although there is a trend of decrease in the incidence of the CL disease in this 8-year period, incidence of the CL disease is still high. This is an alarming condition and careful planning for control and prevention of the disease is highly recommended.


Assuntos
Doenças Endêmicas , Leishmaniose Cutânea/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Crioterapia , Doenças Endêmicas/estatística & dados numéricos , Feminino , Humanos , Incidência , Lactente , Irã (Geográfico)/epidemiologia , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/terapia , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/uso terapêutico , Microscopia , Pessoa de Meia-Idade , Ocupações , Estações do Ano , Software , Adulto Jovem
11.
PLoS Negl Trop Dis ; 13(6): e0007423, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31188834

RESUMO

BACKGROUND: The control of cutaneous leishmaniasis (CL) is facilitated by knowledge of factors associated with the treatment failures in endemic countries. The aim of this evaluation was to identify the potential risk determinants which might affect the significance of demographic and clinical characteristics for the patients with anthroponotic CL (ACL) and the outcome of meglumine antimoniate (MA) (Glucantime) treatment. METHODOLOGY/PRINCIPAL FINDINGS: This current was executed as a cohort spanning over a period of 5 years which centered in southeastern part of Iran. Altogether, 2,422 participants were evaluated and 1,391 eligible volunteer patients with ACL caused by Leishmania tropica were included. Overall, 1,116 (80.2%) patients received MA intraleisionally (IL), once a week for 12 weeks along with biweekly cryotherapy, while 275 (19.8%) patients received MA alone (20 mg/kg/day for 3 weeks) (intramuscular, IM). The treatment failure rate in ACL patients was 11% using IL combined with cryotherapy plus IM alone, whilst 9% and 18.5% by IL along with cryotherapy or IM alone, respectively. Multivariate logistic regression model predicted 5 major associated-risk determinants including male (odds ratio (OR) = 1.54, confidence interval (CI) = 1.079-2.22, p = 0.018), lesion on face (OR = 1.574, CI = 1.075-2.303, p = 0.02), multiple lesions (OR = 1.446, CI = 1.008-2.075, p = 0.045), poor treatment adherence (OR = 2.041, CI = 1.204-3.46, p = 0.008) and disease duration > 4 months (OR = 2.739, CI = 1.906-3.936, p≤0.001). CONCLUSIONS/SIGNIFICANCE: The present study is the original and largest cohort of ACL patients who treated with MA. A comprehensive intervention and coordinated action by the health authorities and policy-makers are crucial to make sure that patients strictly follow medical instructions. Early detection and effective therapy < 4 months following the onset of the lesion is critical for successful treatment of the patients. Since a significant number of patients are still refractory to MA, reducing man-vector exposure and development of new effective alternative drugs are essential measures against ACL due to L. tropica.


Assuntos
Antiprotozoários/uso terapêutico , Leishmania tropica/isolamento & purificação , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Antimoniato de Meglumina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Crioterapia/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Leishmaniose Cutânea/microbiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Falha de Tratamento , Adulto Jovem
12.
J Vet Cardiol ; 23: 32-37, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31174727

RESUMO

A 4-year-old crossbreed dog presented with a two-day history of lethargy and abdominal effusion. Physical examination and echocardiography revealed pericardial effusion with cardiac tamponade. Pericardiocentesis was performed. Intracytoplasmic Leishmania amastigotes were found on cytological examination of the pericardial fluid. The animal was treated with N-methylglucamine antimoniate and allopurinol. After an initial favorable response, cardiac tamponade reoccurred one month later. The dog died during a pericardiectomy four months after the initial diagnosis. Histology confirmed the presence of chronic pericarditis. The presence of Leishmania amastigotes on cytological examination of pericardial effusion suggests a possible association between canine leishmaniasis and chronic pericarditis. This finding also supports the importance of cytological examination of pericardial fluid in areas endemic for canine leishmaniasis.


Assuntos
Doenças do Cão/parasitologia , Leishmaniose/veterinária , Derrame Pericárdico/veterinária , Alopurinol/uso terapêutico , Animais , Antiprotozoários/uso terapêutico , Tamponamento Cardíaco/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/fisiopatologia , Cães , Ecocardiografia/veterinária , Leishmania/isolamento & purificação , Leishmaniose/complicações , Leishmaniose/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/parasitologia , Líquido Pericárdico/parasitologia
14.
Epidemiol Health ; 41: e2019011, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30999735

RESUMO

Cutaneous leishmaniasis (CL) is most common form of leishmaniasis and is characterized by ulcerative skin lesions. The objective of this study was to conduct a systematic review and meta-analysis of clinical trials that compared the efficacy of miltefosine and glucantime for the treatment of CL. We searched the following databases: Cochrane, PubMed, Embase, Scopus, Web of Science, ProQuest, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform search portal of World Health Organization, Sid, Irandoc, Magiran, and clinicaltrials.gov. We used keywords including "miltefosine," "glucantime," and "Leishmania." The quality of studies was assessed using the Cochrane risk of bias tool. A random-effects model was employed for the analysis. We assessed heterogeneity by the chi-square test and the I2 index statistic. When heterogeneity was present, meta-regression analyses were performed. The Egger method was used to assess publication bias; when it was significant, the trim-and-fill method was used to test and adjust for publication bias. A total of 1,570 reports were identified, of which 10 studies were included in the meta-analysis. In the meta-analysis, there was no significant difference between the efficacy of miltefosine and glucantime; however, subgroup analysis showed that, regarding parasite species other than Leishmania braziliensis, miltefosine was significantly superior to glucantime (intention to treat; relative risk, 1.15; 95% confidence interval, 1.01 to 1.32). In the meta-regression, only the glucantime injection type was significant at the p=0.1 level. The Egger test found statistically significant publication bias; however, including the 3 missing studies in the trim-and-fill analysis did not change the results. This meta-analysis found that miltefosine seems to be more effective than glucantime, at least in species other than L. braziliensis, for treating CL.


Assuntos
Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Fosforilcolina/análogos & derivados , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Fosforilcolina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Exp Parasitol ; 200: 30-35, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30898544

RESUMO

Topical treatment of cutaneous leishmaniasis has demonstrated appropriate alternative for reducing toxicity of conventional treatments, improving patients' compliance and reducing treatment costs. Furthermore, outbreak of cutaneous leishmaniasis in war and conflict zones emerges finding an effective, economical and user-friendly treatment. In the context of liposomal topical drug delivery, we developed and characterized meglumine antimoniate (MA) loaded liposomes and investigated their effectiveness in topical treatment of cutaneous leishmaniasis. Previously, we showed the promising use of liposomal formulation of MA in treatment of cutaneous leishmaniasis in BALB/c mice. Here, we included Stearylamine (SA) in liposomes' structure which has antileishmanial activity by itself. . Size and encapsulation efficiency of liposomes were measured and in vitro permeation was performed using mice model. In vitro toxicity of liposomes was measured against leishmania promastigotes and amastigotes. Liposomes were used topically twice a day for 4 weeks to treat leishmania lesions in BALB\c mice model. In vitro permeation study showed liposomal formulations improved the percent of MA permeation compared with MA-cream. Promastigotes and amastigotes assay results showed significant enhanced toxicity in Liposomal-MA containing SA compared to Lip-MA. In BALB\c mice model of cutaneous leishmaniasis, liposomal groups exhibited significantly smaller lesion size compared to control groups (p < 0.01). In addition, the spleen parasite burden was significantly (P < 0.01) lower in mice treated with selected liposomal MA than in mice treated with PBS, control liposomes and MA cream. The results of this study showed that SA-liposomes encapsulated with MA might be useful as a candidate for the topical treatment of CL which merit further investigation.


Assuntos
Aminas/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Análise de Variância , Animais , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Feminino , Lipossomos , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Coelhos , Baço/parasitologia
17.
Vet J ; 245: 22-28, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30819422

RESUMO

The objective of this study was to compare changes in serum concentrations of acute phase proteins (APPs) and paraoxanase (PON-1) in response to two treatments in dogs with leishmaniosis (CanL). For this purpose, 20 dogs with CanL were assigned to two treatment groups: antimonial plus allopurinol (Group G, n=12) and miltefosine plus allopurinol (Group M, n=8). Serum concentrations of PON-1 and APPs including C-reactive protein, haptoglobin (Hp), ferritin (Ft) and albumin were monitored over a period of 3 months after treatment. At the beginning of the study (day 0), most of the dogs had APP abnormalities. None of the variables differed significantly between groups in the first or subsequent visits. There was a significantly higher reduction in serum Ft in Group G than in Group M from day 0 to day 30 (P=0.0085), and also from day 0 to day 90 (P=0.0214). There was a higher increase in serum PON-1 in Group G than in than Group M from day 0 to day 30 (P=0.0039), and also from day 0 to day 90 (P=0.0404). This is the first report of APPs in dogs with natural clinical leishmaniosis treated with miltefosine. There was faster resolution of serum APP concentrations in dogs treated with antimonials (P<0.05).


Assuntos
Proteínas da Fase Aguda/análise , Antiprotozoários/uso terapêutico , Doenças do Cão/sangue , Doenças do Cão/tratamento farmacológico , Leishmaniose Visceral/veterinária , Alopurinol/uso terapêutico , Animais , Arildialquilfosfatase/análise , Cães , Leishmania infantum , Leishmaniose Visceral/sangue , Leishmaniose Visceral/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico
18.
Int Immunopharmacol ; 69: 321-327, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30771740

RESUMO

The objective of the present study was to compare the host's immune responses between unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis (ACL) treated by meglumine antimoniate. A case-control study was carried out in an endemic focus in Iran. Blood samples were taken from patients and peripheral blood mononuclear cells (PBMCs) were isolated. Two wells were considered for each isolate of unresponsive and responsive patients; one was exposed to L. tropica (Lt-stimulated cells) and the other remained non-exposed (non-stimulated cells). After 24 h of incubation, whole RNA was extracted from each sample. Real-time quantitative PCR was carried out to confirm the differences in expression levels of IL-12 P40, IFN-γ, IL-1ß, IL-4 and IL-10 among isolates. Data were analyzed and P < 0.05 was considered to be statistically significant. In our study, Lt-stimulated cells and non-stimulated cells in unresponsive groups demonstrated significantly lower expression levels of IL-1ß, IL-12 P40 and IFN-γ genes and higher expression levels of IL-4 and IL-10 genes, compared to Lt-stimulated cells and non-stimulated cells in responsive groups. There was a negative correlation between IL-12 P40 with IL-10 and IL-1ß with IL-10 in ACL Lt-stimulated cells in unresponsive group, while a positive correlation between IL-12 P40 with IL-1ß and IL-12 P40 with IFN-γ in ACL Lt-stimulated cells in responsive group. Probably, different immune responses caused by various factors play a major role in the pathogenesis and development of unresponsiveness in ACL patients. The profile and timing of cytokine production correlated well with the treatment outcome of Leishmania infection.


Assuntos
Antiprotozoários/uso terapêutico , Leishmania tropica/fisiologia , Leishmaniose Cutânea/tratamento farmacológico , Leucócitos Mononucleares/efeitos dos fármacos , Antimoniato de Meglumina/uso terapêutico , Estudos de Casos e Controles , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Doenças Endêmicas , Feminino , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Irã (Geográfico) , Leucócitos Mononucleares/fisiologia , Masculino , Células Th1/imunologia , Resultado do Tratamento
19.
J Eur Acad Dermatol Venereol ; 33(9): 1781-1783, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30801816

RESUMO

BACKGROUND: The polymorphic clinical presentations of schistosomiasis and leishmaniasis allow their inclusion in the differential diagnoses of several conditions. Although an overlap in distribution of these diseases has been reported in endemic areas, coinfection with cutaneous schistosomiasis and cutaneous leishmaniasis in the same patient is rare. OBJECTIVES: We report an unusual case of concomitant cutaneous schistosomiasis and cutaneous leishmaniasis. Actions for the management and diagnosis were proposed. METHODS: A patient presented with cutaneous lesions on the abdomen and left elbow. The presence of degenerated ova of Schistosoma mansoni in the skin biopsy led to perform a complementary investigation with immunohistochemical techniques, rectal biopsy and abdominal ultrasonography. After the left elbow lesions had failed to improve after several weeks of standard treatment, a new biopsy was performed and led to diagnosis of another infection. RESULTS: The patient lived in an endemic area for two infectious diseases (schistosomiasis and leishmaniasis). Biopsies revealed chronic granulomatous dermatitis. Degenerated S. mansoni eggs were found in the abdominal lesion and in a rectal biopsy specimen. Ultrasonography revealed hepatic involvement. Despite combination treatment with oxamniquine and praziquantel, a cutaneous lesion persisted on the left elbow; a new biopsy revealed amastigote forms of Leishmania. The patient was successfully treated with intramuscular and intralesional meglumine antimoniate. CONCLUSIONS: The presence of a similar granulomatous infiltrate in lesions caused by the two different infectious agents led to a delay in the diagnosis of cutaneous leishmaniasis. This report serves as a warning of the unusual possibility of cutaneous schistosomiasis and leishmaniasis coinfection in an endemic area.


Assuntos
Coinfecção/diagnóstico , Leishmaniose Cutânea/diagnóstico , Esquistossomose/diagnóstico , Dermatopatias Parasitárias/diagnóstico , Adulto , Antiprotozoários/uso terapêutico , Biópsia , Coinfecção/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Esquistossomose/tratamento farmacológico , Dermatopatias Parasitárias/tratamento farmacológico
20.
Trop Med Int Health ; 24(4): 380-391, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30681239

RESUMO

OBJECTIVES: Meglumine antimoniate (MA; Glucantime®), the 80-year-old first-line systemic treatment for all forms of American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) amazonensis, is highly toxic, presents adverse side-effects and may not attain clinical and parasitological cure. This critical review examines the necessity for intramuscular/intravenous administration of MA, the alternatives to this approach, and the possibilities of developing affordable, accessible and non-toxic drugs or new delivery methods. METHOD: PubMed searches were performed using the terms 'cutaneous leishmaniasis' or 'American tegumentary leishmaniasis' in combination with 'meglumine antimoniate' or 'N-methyl glucamine' or 'drug repositioning' or 'nanotechnology'. Searches covered a period of 20 years of peer reviewed journals and technical bulletins. We explored the mode of action, pharmacokinetics, toxicity and efficacy of MA, evaluated the progress of ATL therapy in Brazil, and examined the potential of drug repositioning and nanotechnology in accelerating the introduction and/or optimisation of an alternative treatment. RESULTS: The evidence suggests that ATL therapy will continue to rely on systemic MA in the foreseeable future even though an intralesional subcutaneous route has evolved over the last 10 years. The chances of developing a novel drug for ATL or a new mode of delivery of MA are low. While MA nanocarriers afford a promising approach, this technology is still in its infancy. A more immediate solution would be the production of a bioequivalent of miltefosine, an efficacious oral agent no longer protected by patent. CONCLUSION: Development of a contemporary treatment requires governmental commitment in bringing together private and public sectors.


Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Fosforilcolina/análogos & derivados , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Brasil , Humanos , Leishmania braziliensis , Leishmania guyanensis , Leishmaniose Cutânea/parasitologia , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Patentes como Assunto , Fosforilcolina/administração & dosagem , Fosforilcolina/uso terapêutico
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