RESUMO
BACKGROUND: In Latin America, cutaneous leishmaniasis primarily affects dispersed rural communities, that have limited access to the public health system and medical attention. Mobile health (mHealth) strategies have shown potential to improve clinical management and epidemiological surveillance of neglected tropical diseases, particularly those of the skin. METHODS: The Guaral +ST app for Android was designed to monitor cutaneous leishmaniasis treatment and assess therapeutic response. We carried out a randomized trial in the coastal municipality of Tumaco in southwestern Colombia, with parallel arms comparing a) follow-up aided by the app to b) standard institution-based follow-up. Treatment was prescribed according to national guidelines. Follow-up of therapeutic response was scheduled at the end of treatment and at 7, 13 and 26 weeks after the start of treatment. The primary endpoint was the proportion of participants who were monitored at or around week 26, allowing outcome and effectiveness of treatment to be determined. RESULTS: Follow-up of treatment and outcome assessment was achieved in significantly more patients in the intervention arm than the controls, Of the 75 participants in the two randomized arms, 74 had information on whether or not treatment was followed and outcome determined at or around week 26. Among these, 26/49 (53.1%) were evaluated in the intervention arm, and none (0/25, 0%) in the control arm (difference = 53.1%, 95% confidence interval 39.1-67.0%, p<0.001). Of the 26 participants evaluated at or around week 26 in the intervention arm, 22 (84.6%) had cured. There were no serious adverse events, nor events of severe intensity among patients monitored by CHW using the app. CONCLUSION: This study provides proof of concept for mHealth to monitor treatment of CL in remote and complex settings, deliver improved care and to provide information to the health system on the effectiveness of treatment as it is delivered to affected populations. CLINICAL TRIAL REGISTRATION: ISRCTN54865992.
Assuntos
Leishmaniose Cutânea , Telemedicina , Humanos , População Rural , Colômbia/epidemiologia , Seguimentos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/terapiaRESUMO
INTRODUCTION: Regional hyperthermia at between 38 and 39.5 °C has been used to treat inflammatory processes and, occasionally, skin infections. In areas where leishmaniasis is endemic, hot compresses are applied as anti-parasitic treatment. OBJECTIVE: To identify the bases of leishmaniasis thermal treatment in order to properly regulate it. METHODS: In vitro-cultured Leishmania mexicana parasites were incubated for variable periods at 37 and then at 25 °C. The parasites were then stained with Annexin V-FITC to detect apoptosis induction and with propidium iodide for viability. Post-treatment growth curves and cell cycle identification with anti-cyclin antibodies were performed. RESULTS: After 30 minutes of exposure to a temperature of 37 °C, a variable proportion of parasites lost their characteristic oval shape and became spherical, without refringence and with condensed nuclei, with these changes suggesting apoptosis, which was confirmed by Annexin V-FITC staining. The number of parasites that underwent apoptosis was proportional to exposure time. Parasites in which apoptosis was observed were stained with anti-cyclin antibodies. CONCLUSIONS: Constant, regulated and physiological elevation of temperature for more than 30 minutes induces apoptosis of in vitro-cultured L. mexicana parasites when they are in an active phase of the cell cycle.
INTRODUCCIÓN: La hipertermia regional entre 38 y 39.5 °C ha sido empleada para tratar procesos inflamatorios y, ocasionalmente, infecciones cutáneas. En zonas endémicas de leishmaniosis se aplican compresas calientes como tratamiento antiparasitario. OBJETIVO: Conocer las bases del tratamiento térmico de la leishmaniosis para regularlo adecuadamente. MÉTODOS: Parásitos Leishmania mexicana cultivados in vitro fueron incubados por periodos variables de 37 °C y después a 25 °C.. Los parásitos se tiñeron con anexina V-FITC y yoduro de propidio para detectar inducción de apoptosis y su viabilidad. Se realizaron curvas de crecimiento postratamiento e identificación del ciclo celular con anticuerpos anticiclinas. RESULTADOS: Después de 30 minutos de exposición a una temperatura de 37 °C, un porcentaje variable de parásitos perdieron su característica forma ovalada y se tornaron esféricos, sin refringencia y con núcleos condensados, cambios que sugirieron apoptosis, la cual fue confirmada mediante tinción con anexina V-FITC. La cantidad de parásitos en proceso de apoptosis fue proporcional al tiempo de exposición. Los parásitos en los que se observó apoptosis se tiñeron con anticuerpos anticiclinas. CONCLUSIONES: La elevación constante, regulada y fisiológica de la temperatura por más de 30 minutos induce apoptosis de parásitos Leishmania mexicana cultivados in vitro, cuando se encuentran en fase activa en el ciclo celular.
Assuntos
Hipertermia Induzida , Leishmania mexicana , Leishmaniose Cutânea , Humanos , Propídio , Leishmaniose Cutânea/terapia , Leishmaniose Cutânea/diagnóstico , ApoptoseRESUMO
We report the novel use of cryosurgery to treat cutaneous feline leishmaniosis (FeL) in a domestic cat from mid-western Venezuela. Amastigotes, evident by microscopy in aspirates from the nodular, erythematous nose lesions, were identified as Leishmania mexicana by cytochrome b gene sequence analysis. Lesions resolved completely without relapse after 14 months.
Nous décrivons une nouvelle utilisation de la cryochirurgie pour traiter la leishmaniose féline cutanée (FeL) chez un chat domestique du centre-ouest du Venezuela. Les amastigotes, observés par microscopie dans les cytoponctions des lésions nodulaires et érythémateuses du nez, ont été identifiés comme Leishmania mexicana par analyse de la séquence du gène du cytochrome b. Les lésions ont complètement disparu sans rechute après 14 mois.
Describimos el uso novedoso de la criocirugía para tratar la leishmaniosis cutánea felina (FeL) en un gato doméstico del medio oeste de Venezuela. Los amastigotes, evidentes por microscopía en los aspirados de las lesiones nasales nodulares eritematosas, se identificaron como Leishmania mexicana mediante el análisis de la secuencia del gen del citocromo b. Las lesiones se resolvieron completamente sin recidiva tras 14 meses.
Neste estudo, relatamos a utilização inédita de criocirurgia para tratar leishmaniose felina cutânea (FeL) em um gato doméstico no centro-oeste da Venezuela. Amastigotas, evidentes à microscopia de aspirados da lesão nodular e eritematosa na região nasal, foram identificadas como Leishmania Mexicana por sequenciamento do gene do citocromo b. As lesões se resolveram completamente sem recidiva após 14 meses.
Assuntos
Doenças do Gato , Leishmania mexicana , Leishmaniose Cutânea , Animais , Doenças do Gato/cirurgia , Gatos , Crioterapia/veterinária , Leishmaniose Cutânea/terapia , Leishmaniose Cutânea/veterináriaRESUMO
BACKGROUND: Neglected tropical diseases (NTDs) such as cutaneous leishmaniasis (CL) are often associated with rural territories and vulnerable communities with limited access to health care services. The objective of this study is to identify the potential determinants of CL care management in the indigenous communities in the rural area of the municipality of Pueblo Rico, through a people-centered approach. METHODS: To achieve this goal, qualitative ethnographic methods were used, and a coding framework was developed using procedures in accordance with grounded theory. RESULTS: Three dimensions that affect access to health care for CL in this population were identified: (1) contextual barriers related to geographic, economic and socio-cultural aspects; (2) health service barriers, with factors related to administration, insufficient health infrastructure and coverage, and (3) CL treatment, which covers perceptions of the treatment and issues related to the implementation of national CL treatment guidelines. This study identified barriers resulting from structural problems at the national level. Moreover, some requirements of the national guidelines for CL management in Colombia impose barriers to diagnosis and treatment. We furthermore identified cultural barriers that influence the perceptions and behavior of the community and health workers. CONCLUSIONS: While the determinants to CL management are multidimensional, the most important barrier is the inaccessibility to CL treatment to the most vulnerable populations and its inadequacy for the socio-territorial setting, as it is not designed around the people, their needs and their context.
Assuntos
Leishmaniose Cutânea , População Rural , Colômbia , Atenção à Saúde , Humanos , Leishmaniose Cutânea/terapia , Pesquisa QualitativaRESUMO
A Leishmaniose Tegumentar Americana (LTA) é uma doença infecciosa, que evolui com destruição tecidual. O tratamento convencional é associado a efeitos adversos graves que podem resultar em abandono da terapia. Objetivo: Mostrar a homeopatia como uma opção terapêutica para o tratamento da LTA sem submeter o paciente aos efeitos deletérios do tratamento convencional. Métodos: Trata-se de um estudo de um caso de leishmaniose tegumentar americana atendido em um consultório particular. O paciente havia sido tratado com homeopatia clássica por um longo tempo. A intervenção foi feita por um medicamento individualizado a cada consulta. Vários medicamentos homeopáticos foram administrados, sendo um de cada vez. Resultados: Todas as manifestações da doença, incluindo a úlcera, foram curadas em 5 meses, sem efeitos colaterais e sem sinais de recaída após 12 anos de seguimento. Conclusão: O tratamento homeopático individualizado isoladamente foi eficaz para curar um caso de LTA em apenas alguns meses e seus efeitos permaneceram após 15 anos de seguimento. Ensaios clínicos controlados randomizados são necessários para demonstrar a eficácia do tratamento homeopático.
American cutaneous leishmaniasis (ACL) is a tissue destructing, potentially disfiguring vector-borne disease. Conventional treatment is associated with severe adverse effects which might result in dropout. Methods: Case report of an ACL patient presenting with a severe leg ulcer. The patient was followed up at a conventional specialized service but received individualized homeopathic treatment alone. Results: All manifestations of disease including the ulcer were healed in 5 months with no side effects and no signs of relapse after 13-year follow up. Conclusion: Individualized homeopathic treatment alone was effective to heal a case of ACL in just few months, the effects lasting after 15-year follow up. Randomized controlled trials are necessary to demonstrate the efficacy of the homeopathic treatment for ACL.
Assuntos
Humanos , Feminino , Adulto , Leishmaniose Cutânea/terapia , HomeopatiaRESUMO
BACKGROUND: Leishmaniasis is a neglected disease caused by Leishmania spp. One of its characteristics is an imbalance of host immune responses to foster parasite survival. In this setting, mesenchymal stromal cells (MSCs) may be a viable therapeutic alternative, given their well-established immunomodulatory potential. In this study, we compared the effects of therapy with bone marrow (BM)- and adipose tissue (AD)-derived MSCs in leishmaniasis caused by Leishmania amazonensis in C57BL/6 mice. After determining the most effective MSC source, we then combined these cells with meglumine antimoniate (a pentavalent antimonial commonly used for the treatment of leishmaniasis) to treat the infected mice. METHODS: In vitro, co-culture of AD-MSCs and BM-MSCs with Leishmania amazonensis-infected macrophages was performed to understand the influence of both MSC sources in infected cells. In vivo, infected C57BL/6 mice were treated with phosphate-buffered saline (PBS), AD-MSCs and BM-MSCs, and then meglumine antimoniate was combined with MSCs from the most effective source. RESULTS: In vitro, co-culture of Leishmania amazonensis-infected macrophages with BM-MSCs, compared to AD-MSCs, led to a higher parasite load and lower production of nitric oxide. Fibroblasts grown in conditioned medium from co-cultures with AD-MSCs promoted faster wound healing. Despite a non-significant difference in the production of vascular endothelial growth factor, we observed higher production of tumor necrosis factor-α and interleukin (IL)-10 in the co-culture with AD-MSCs. In vivo, treatment of infected mice with BM-MSCs did not lead to disease control; however, the use of AD-MSCs was associated with partial control of lesion development, without significant differences in the parasite load. AD-MSCs combined with meglumine antimoniate reduced lesion size and parasite load when compared to PBS and AD-MSC groups. At the infection site, we detected a small production of IL-10, but we were unable to detect production of either IL-4 or interferon-γ, indicating resolution of infection without effect on the percentage of regulatory T cells. CONCLUSION: Combination treatment of cutaneous leishmaniasis with AD-MSCs and meglumine antimoniate may be a viable alternative.
Assuntos
Leishmania , Leishmaniose Cutânea , Células-Tronco Mesenquimais , Animais , Leishmaniose Cutânea/terapia , Antimoniato de Meglumina , Camundongos , Camundongos Endogâmicos C57BL , Carga Parasitária , Fator A de Crescimento do Endotélio VascularRESUMO
In cutaneous leishmaniasis endemic areas it is a common practice for patients to manipulate their lesions with traditional treatments as a first therapeutic option. A case series study was conducted in order to describe the frequency and the variations of the patient manipulation of cutaneous leishmaniasis lesions at the Cayetano Heredia Hospital. The study included 124 patients with cutaneous leishmaniasis. From the patient population it was found that 54% (67/124) manipulated their lesions. Of this, 92.5% (62/67) did so with chemicals, and 43.3% (29/67) with plants. The most frequent local changes reported by patients were increased lesion size in 35.8% (24/67) and increased inflammation in 28.4% (19/67). Manipulation by patients decreased the positivity of the parasitological diagnosis in those patients with ulcerative lesions.
En áreas endémicas de leishmaniasis cutánea es común que los pacientes manipulen sus lesiones con tratamientos tradicionales como primera opción terapéutica. Con el objetivo de describir la frecuencia y los cambios de la manipulación de lesiones de leishmaniasis cutánea de pacientes en el Hospital Cayetano Heredia, se realizó un estudio tipo serie de casos. Se incluyeron 124 pacientes con leishmaniasis cutánea. El 54% (67/124) manipuló sus lesiones; el 92,5% (62/67) lo hizo con productos químicos, y el 43,3% (29/67), con plantas. Los cambios locales más frecuentemente reportados por los pacientes fueron aumento de tamaño de la lesión en el 35,8% (24/67) e incremento de inflamación en el 28,4% (19/67). La manipulación disminuyó la positividad del diagnóstico parasitológico en aquellos pacientes con lesiones ulcerativas.
Assuntos
Leishmaniose Cutânea , Medicina Tradicional , Hospitais , Humanos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/terapia , Medicina Tradicional/estatística & dados numéricos , Peru/epidemiologia , Resultado do TratamentoRESUMO
The aims of this study were to describe a smartphone app aimed at healthcare professionals who work in areas endemic for visceral and tegumentary leishmaniases, and to report the user's perception of the app in these areas. The software, called LeishCare®, has the following features: data registration, image filter to record the evolution of skin lesions using photos, calculation of a score set to identify the risk of death from visceral leishmaniasis, and guides to the diseases. LeishCare® was made available to healthcare professionals in endemic municipalities in Brazil, and the perception of potential users was evaluated at baseline and after 6 and 12 months. In the first meeting, 96 (94.1%) of the 102 professionals who knew the app reported positive expectations for its use. The installation of LeishCare® on the individual device and the evaluation of user perception were completed at 6 months with 16 users and at 12 months with 20 users. More than 90% of the professionals evaluated in both assessments found the information of the app useful. The features related to the calculation of visceral leishmaniasis severity score, and the guides to leishmaniases were the most frequently accessed. Users reported competence gain attributed to the app for all items evaluated. In conclusion, LeishCare® was found to be a promising tool to help healthcare professionals in endemic areas with leishmaniasis management.
Assuntos
Leishmaniose Cutânea/terapia , Leishmaniose Visceral/terapia , Aplicativos Móveis , Smartphone , Atitude do Pessoal de Saúde , Brasil , Comportamento do Consumidor , Gerenciamento Clínico , Diagnóstico Precoce , Intervenção Médica Precoce , Doenças Endêmicas , Humanos , Disseminação de Informação , Leishmaniose Cutânea/diagnóstico , Leishmaniose Visceral/diagnóstico , Fotografação , Medição de Risco , SoftwareRESUMO
RESUMEN En áreas endémicas de leishmaniasis cutánea es común que los pacientes manipulen sus lesiones con tratamientos tradicionales como primera opción terapéutica. Con el objetivo de describir la frecuencia y los cambios de la manipulación de lesiones de leishmaniasis cutánea de pacientes en el Hospital Cayetano Heredia, se realizó un estudio tipo serie de casos. Se incluyeron 124 pacientes con leishmaniasis cutánea. El 54% (67/124) manipuló sus lesiones; el 92,5% (62/67) lo hizo con productos químicos, y el 43,3% (29/67), con plantas. Los cambios locales más frecuentemente reportados por los pacientes fueron aumento de tamaño de la lesión en el 35,8% (24/67) e incremento de inflamación en el 28,4% (19/67). La manipulación disminuyó la positividad del diagnóstico parasitológico en aquellos pacientes con lesiones ulcerativas.
ABSTRACT In cutaneous leishmaniasis endemic areas it is a common practice for patients to manipulate their lesions with traditional treatments as a first therapeutic option. A case series study was conducted in order to describe the frequency and the variations of the patient manipulation of cutaneous leishmaniasis lesions at the Cayetano Heredia Hospital. The study included 124 patients with cutaneous leishmaniasis. From the patient population it was found that 54% (67/124) manipulated their lesions. Of this, 92.5% (62/67) did so with chemicals, and 43.3% (29/67) with plants. The most frequent local changes reported by patients were increased lesion size in 35.8% (24/67) and increased inflammation in 28.4% (19/67). Manipulation by patients decreased the positivity of the parasitological diagnosis in those patients with ulcerative lesions.
Assuntos
Humanos , Leishmaniose Cutânea , Medicina Tradicional , Peru/epidemiologia , Resultado do Tratamento , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/terapia , Leishmaniose Cutânea/epidemiologia , Hospitais , Medicina Tradicional/estatística & dados numéricosRESUMO
Physical exercise has been described as an important tool in the prevention and treatment of numerous diseases as it promotes a range of responses and adaptations in several biological systems, including the immune system. Studies on the effect of exercise on the immune system could play a critical role in improving public health. Current literature suggests that moderate intensity exercise can modulate the Th1/Th2 dichotomy directing the immune system to a Th1 cellular immune response, which favors the resolution of infections caused by intracellular microorganisms. Leishmaniasis is a group of diseases presenting a wide spectrum of clinical manifestations that range from self-limiting lesions to visceral injuries whose severity can lead to death. The etiological agents responsible for this group of diseases are protozoa of the genus Leishmania. Infections by the parasite Leishmania major in mice (Balb/c) provide a prototype model for the polarization of CD4+ T cell responses of both Th1 (resistance) or Th2 (susceptibility), which determines the progression of infections. The aim of this study was to evaluate the effect of exercise on the development of L. major experimental infections by scanning the pattern of immune response caused by exercise. Groups of Balb/c mice infected with L. major were divided into groups that preformed a physical exercise of swimming three times a week or were sedentary along with treatment or not with the reference drug, meglumine antimoniate. Animals in groups submitted to physical exercise did not appear to develop lesions and presented a significantly lower parasite load independent of drug treatment. They also showed a positive delayed hypersensitivity response to a specific Leishmania antigen compared to control animals. The IFN-γ/IL-4 and IFN-γ/IL10 ratios in trained animals were clearly tilted to a Th1 response in lymph node cells. These data suggest that moderate intensity exercise is able to modulate the Th1 response that provides a protective effect against the development of leishmanial lesions.
Assuntos
Terapia por Exercício/métodos , Imunomodulação , Leishmania major/imunologia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/terapia , Condicionamento Físico Animal , Animais , Citocinas/análise , Modelos Animais de Doenças , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Camundongos Endogâmicos BALB C , Carga Parasitária , Células Th1/imunologia , Resultado do TratamentoRESUMO
Objective: In this study, we evaluated the effectiveness of photodynamic therapy (PDT) for the treatment of experimental cutaneous leishmaniasis (CL) and the profile of macrophages activation markers. Background: Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania. CL is caused by Leishmania major in the old world and by Leishmania braziliensis in the Americas. Considering the targeted organs, PDT may constitute a valuable therapeutic intervention. Macrophages are the host cells of Leishmania in mammals and may be classified into type M1 or M2 depending on the pattern of activation. Methods: BALB/c mice were infected in the foot pad with 1 × 106 amastigotes of L. braziliensis and treated with 5-aminolevulinic acid (5-ALA), visible light, or 5-ALA-PDT. The ex vivo mRNA expression levels of interleukin-10, tumor necrosis factor-α (TNF-α), arginase-1, heme oxygenase ( Hmox), and induced nitric oxide synthase (iNOS) were quantities as markers of macrophage activation with distinct ability to kill intracellular parasite. Results: The parasite load decreased significantly in the group treated with PDT compared with the other groups. The iNOS relative mRNA was higher in the group treated with PDT and light only compared with the group without treatment, whereas iNOS/arginase ratio was significantly higher only in the PDT group. The expression of TNF-α was significantly higher in 5-ALA and light compared with PDT and control group. No significant difference was observed in the expression of the other markers evaluated. Conclusions: Both, light and 5-ALA-PDT were able to upregulate iNOS expression only; 5-ALA-PDT was able to reduce parasite burden. The increase in the iNOS levels suggests it might participate in the antimicrobial mechanisms triggered by 5-ALA-PDT; although parasite death mechanism was not completely clarified, the results presented in this study suggest that macrophage activation may contribute to parasite control.
Assuntos
Ácido Aminolevulínico/uso terapêutico , Leishmaniose Cutânea/terapia , Ativação de Macrófagos/efeitos da radiação , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Modelos Animais de Doenças , Interleucina-10/metabolismo , Leishmaniose Cutânea/metabolismo , Leishmaniose Cutânea/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Local therapies have been proposed as safe and effective alternatives to systemic drugs in cutaneous leishmaniasis (CL), especially among less severe cases. However, they are not widely available and used in endemic places, including Colombia, which has a high burden of disease. Further complicating the uptake of local therapies is that different treatment guidelines have been established by the World Health Organization (WHO) and Pan American Health Organization (PAHO). Using data from a large referral center in Colombia, we determined the proportion of patients who would be eligible for and potentially benefit from local therapies according to both international guidelines. The sample included 1,891 confirmed cases of CL aged ≥ 12 years, mostly infected with Leishmania Viannia panamensis (91%, n = 601/660), between 2004 and 2014. Overall, 57% of the sample had one lesion, whereas another 31% had two to three lesions. For 74% of patients, all lesions were in an area other than head or neck. The maximum lesion size was ≤ 3 cm for 58% and < 5 cm for 88% of the sample. Based on our data, up to 56% of patients could have been eligible for local therapies according to the WHO criteria. By contrast, only 23% were eligible according to the more restrictive PAHO criteria. Regardless, these data suggest that a substantial proportion of CL patients in Colombia may benefit from local therapies given their relatively mild presentation of disease and low risk of complications. Individualized risk-benefit assessment and guideline adjustments may increase local therapy eligibility and benefit a large number of patients.
Assuntos
Antimônio/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania braziliensis/efeitos dos fármacos , Leishmania guyanensis/efeitos dos fármacos , Leishmaniose Cutânea/terapia , Paromomicina/uso terapêutico , Pentamidina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colômbia/epidemiologia , Estudos Transversais , Crioterapia/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Leishmania braziliensis/crescimento & desenvolvimento , Leishmania braziliensis/patogenicidade , Leishmania guyanensis/crescimento & desenvolvimento , Leishmania guyanensis/patogenicidade , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Índice de Gravidade de DoençaRESUMO
L. (viannia) braziliensis infection causes American Tegumentary Leishmaniasis (ATL), with prolonged time to healing lesions. The potent inflammatory response developed by the host is important to control the parasite burden and infection however an unbalanced immunity may cooperate to the tissue damage observed. The range of mechanisms underlying the pathological responses associated with ATL still needs to be better understood. That includes epigenetic regulation by non-coding MicroRNAs (miRNAs), non-coding sequences around 22 nucleotides that act as post-transcriptional regulators of RNAs encoding proteins. The miRNAs have been associated with diverse parasitic diseases, including leishmaniasis. Here we evaluated miRNAs that targeted genes expressed in cutaneous leishmaniasis lesions (CL) by comparing its expression in both CL and normal skin obtained from the same individual. In addition, we evaluated if the miRNAs expression would be correlated with clinical parameters such as therapeutic failure, healing time as well as lesion size. The miR-361-3p and miR-140-3p were significantly more expressed in CL lesions compared to normal skin samples (p = 0.0001 and p < 0.0001, respectively). In addition, the miR-361-3p was correlated with both, therapeutic failure and healing time of disease (r = 0.6, p = 0.003 and r = 0.5, p = 0.007, respectively). In addition, complementary analysis shown that miR-361-3p is able to identify with good sensitivity (81.2%) and specificity (100%) patients who tend to fail initial treatment with pentavalent antimonial (Sbv). Finally, the survival analysis considering "cure" as the endpoint showed that the higher the expression of miR-361-3p, the longer the healing time of CL. Overall, our data suggest the potential of miR-361-3p as a prognostic biomarker in CL caused by L. braziliensis.
Assuntos
Leishmania braziliensis/fisiologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose Cutânea/genética , MicroRNAs/genética , Pele/patologia , Adolescente , Adulto , Biomarcadores , Feminino , Granzimas/genética , Humanos , Leishmaniose Cutânea/mortalidade , Leishmaniose Cutânea/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pele/parasitologia , Análise de Sobrevida , Resultado do Tratamento , Fator de Necrose Tumoral alfa/genética , Cicatrização/genética , Adulto JovemRESUMO
Se estudió a una mujer de 19 años, con embarazo de cuatro meses, que presentaba cuatro úlceras cutáneas de tres meses de evolución, diagnosticadas por biopsia como leishmaniasis cutánea. El frotis directo y la leishmanina fueron negativos. Dado que todos los medicamentos usuales para la leishmaniasis cutánea están contraindicados en el embarazo, la paciente no recibió tratamiento, aunque curó espontáneamente durante el embarazo. Se cree que la leishmaniasis cutánea no tiene peligro para la mujer embarazada y que no hay transmisión de la madre al feto en el humano, aunque se ha detectado en animales en condiciones experimentales. La paciente tuvo un parto sin complicaciones y la condición de salud tanto de ella como de su hijo era normal a los dos años de seguimiento.
We studied a 19-year-old woman, with a 4-month pregnancy who presented with four cutaneous leg ulcers of three months of evolution diagnosed by biopsy as cutaneous leishmaniasis. Direct smear and the leishmanin skin test were negative. Since all the usual medications for cutaneous leishmaniasis are contraindicated in pregnancy, she did not receive any treatment but cured spontaneously of her lesions during pregnancy. It is believed that cutaneous leishmaniasis does not carry danger for pregnant women and that there is no maternal-fetal transmission in humans, though it occurs in experimental animals. The patient gave birth without complications and both she and her son remained normal after two years of follow-up.
Assuntos
Gravidez , Leishmaniose Cutânea/terapia , Transmissão Vertical de Doenças Infecciosas , Hipertermia InduzidaRESUMO
BACKGROUND: Pentavalent antimonials remain as the standard drugs in the treatment of cutaneous leishmaniosis. The high cost, difficult administration, long treatment time, toxicity and increasing morbidity are factors that limit the use of these drugs. OBJECTIVES: To describe the response to radiofrequency thermotherapy in the treatment of localized cutaneous leishmaniasis in Brazil, and to evaluate its safety and tolerability. METHODS: We conducted a non-comparative open trial with a total of 15 patients confirmed to have cutaneous leishmaniasis on parasitological examination. A single radiofrequency thermotherapy session at 50ºC for 30 seconds was applied to the lesion and its edges. In patients with more than one lesion, only the largest one was treated initially. If after 30 days there was no evidence of healing, the smaller lesion was also treated with thermotherapy. Clinical cure was defined as visible healing for three months after treatment. The patients were followed-up for six months and there was no follow-up loss. RESULTS: Of all 23 lesions, only two evolved to complete healing without the need of treatment. Of 21 lesions, 18 (85.7%) achieved full healing. The main observed side effects were itching, burning sensation, pain and blisters. STUDY LIMITATIONS: Sample with a small number of patients and short follow-up. CONCLUSION: Thermotherapy can be considered a therapeutic alternative in localized cutaneous leishmaniasis, especially in cases of single cutaneous lesions and with formal contraindications to conventional treatment with pentavalent antimonials.
Assuntos
Antiprotozoários/uso terapêutico , Hipertermia Induzida/métodos , Leishmaniose Cutânea/terapia , Adolescente , Adulto , Idoso , Antiprotozoários/efeitos adversos , Brasil , Intervalos de Confiança , Estudos Controlados Antes e Depois , Resistência a Medicamentos , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Hipertermia Induzida/normas , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , Masculino , Pessoa de Meia-Idade , Ondas de Rádio , Resultado do Tratamento , Adulto JovemRESUMO
Abstract: BACKGROUND: Pentavalent antimonials remain as the standard drugs in the treatment of cutaneous leishmaniosis. The high cost, difficult administration, long treatment time, toxicity and increasing morbidity are factors that limit the use of these drugs. OBJECTIVES: To describe the response to radiofrequency thermotherapy in the treatment of localized cutaneous leishmaniasis in Brazil, and to evaluate its safety and tolerability. METHODS: We conducted a non-comparative open trial with a total of 15 patients confirmed to have cutaneous leishmaniasis on parasitological examination. A single radiofrequency thermotherapy session at 50ºC for 30 seconds was applied to the lesion and its edges. In patients with more than one lesion, only the largest one was treated initially. If after 30 days there was no evidence of healing, the smaller lesion was also treated with thermotherapy. Clinical cure was defined as visible healing for three months after treatment. The patients were followed-up for six months and there was no follow-up loss. RESULTS: Of all 23 lesions, only two evolved to complete healing without the need of treatment. Of 21 lesions, 18 (85.7%) achieved full healing. The main observed side effects were itching, burning sensation, pain and blisters. STUDY LIMITATIONS: Sample with a small number of patients and short follow-up. CONCLUSION: Thermotherapy can be considered a therapeutic alternative in localized cutaneous leishmaniasis, especially in cases of single cutaneous lesions and with formal contraindications to conventional treatment with pentavalent antimonials.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Leishmaniose Cutânea/terapia , Hipertermia Induzida/métodos , Antiprotozoários/uso terapêutico , Ondas de Rádio , Brasil , Resistência a Medicamentos , Intervalos de Confiança , Resultado do Tratamento , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/tratamento farmacológico , Estudos Controlados Antes e Depois , Hipertermia Induzida/efeitos adversos , Hipertermia Induzida/normas , Antiprotozoários/efeitos adversosRESUMO
OBJECTIVE: To document the sources of heterogeneity in outcomes and shortcomings in trial designs reported by previous systematic reviews. METHODS: Systematic review of clinical trials of CL treatments published since 1991, to assess and compare eligibility criteria and outcome measures in trials (any type of treatment) of CL (any form) reported before and after the publication of the CONSORT statement. RESULTS: We identified 106 eligible trials published between 1991 and 2015, 74% after the 2001 CONSORT statement; 58% (n = 63) were on Old-World CL and 37% (n = 40) in New-World CL; overall, 11 531 patients enrolled in 243 treatment groups on 30 different treatments. Both requirements and definitions for eligibility and outcome criteria varied. Compliance with CONSORT requirements increased for studies published after the 2010 update. As for entry criteria, 94% of studies had a requirement for sex (74% of those enrolling also women excluded those who were pregnant or lactating), 69% for age (variable age ranges), 99% parasitological confirmation, 43% prior duration of illness (14% excluded cases with previous episodes), 46% defined the number, 28% the size and 13% the type of lesions (27% with restrictions as to their anatomical location). Follow-up ranged 1-24 months, with 14% and 91% of studies, respectively, having defined initial and final cure. CONCLUSIONS: This review documents changes in reporting before and after the publication of the CONSORT statement. Lack of standardisation, compounded with the small number of trials relative to the magnitude of the disease in its multiple forms, and with the range of treatments tested explains why evidence to inform treatment guidelines is generally weak for CL. Adopting standardised methodologies will improve the quality and consistency of clinical trials, and ultimately yield better treatments for CL.
Assuntos
Ensaios Clínicos como Assunto , Leishmaniose Cutânea/terapia , Avaliação de Resultados em Cuidados de Saúde/normas , Fatores Etários , Ensaios Clínicos como Assunto/normas , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Our aim was to examine histopathological changes in three chronic wounds, and to assess whether the application of negative pressure wound therapy (NPWT) changes the wound bed environment. METHOD: - Results: We recruited three patients were recruited who had a non-healing wounds in excess of eight weeks. Histopathological changes in the wound bed supported the evidence that NPWT changes the wound bed environment by reducing inflammatory damage and facilitating wound bed perfusion with angiogenesis. CONCLUSION: We suggest that NPWT is a valuable adjunct to aid chronic wound healing. In this case series, we observed histopathological changes and improvement in the wounds, following one week's treatment with NPWT. Further analysis should be done to demonstrate any interaction between the cells involved in the wound healing process is enhanced, growth factor performance is optimised and cell migration is achieved following NPWT, in order to facilitate the healing process.
Assuntos
Pé Diabético/terapia , Úlcera da Perna/terapia , Leishmaniose Cutânea/terapia , Tratamento de Ferimentos com Pressão Negativa , Adulto , Idoso , Pé Diabético/enfermagem , Feminino , Humanos , Úlcera da Perna/enfermagem , Leishmaniose Cutânea/enfermagem , Masculino , Pessoa de Meia-Idade , CicatrizaçãoRESUMO
BACKGROUND: Cutaneous leishmaniasis causes a high disease burden in Colombia, and available treatments present systemic toxicity, low patient compliance, contraindications, and high costs. The purpose of this study was to estimate the cost-effectiveness of thermotherapy versus Glucantime in patients with cutaneous leishmaniasis in Colombia. METHODS: Cost-effectiveness study from an institutional perspective in 8133 incident cases. Data on therapeutic efficacy and safety were included, calculating standard costs; the outcomes were disability adjusted life years (DALYs) and the number of patients cured. The information sources were the Colombian Public Health Surveillance System, disease burden studies, and one meta-analysis of controlled clinical trials. Incremental cost-effectiveness was determined, and uncertainty was evaluated with tornado diagrams and Monte Carlo simulations. RESULTS: Thermotherapy would generate costs of US$ 501,621; the handling of adverse effects, US$ 29,224; and therapeutic failures, US$ 300,053. For Glucantime, these costs would be US$ 2,731,276, US$ 58,254, and US$ 406,298, respectively. With thermotherapy, the cost would be US$ 2062 per DALY averted and US$ 69 per patient cured; with Glucantime, the cost would be US$ 4241 per DALY averted and US$ 85 per patient cured. In Monte Carlo simulations, thermotherapy was the dominant strategy for DALYs averted in 67.9% of cases and highly cost-effective for patients cured in 72%. CONCLUSION: In Colombia, thermotherapy can be included as a cost-effective strategy for the management of cutaneous leishmaniasis. Its incorporation into clinical practice guidelines could represent savings of approximately US$ 10,488 per DALY averted and costs of US$ 116 per additional patient cured, compared to the use of Glucantime. These findings show the relevance of the incorporation of this treatment in our country and others with similar parasitological, clinical, and epidemiological patterns.
Assuntos
Hipertermia Induzida/economia , Leishmaniose Cutânea/terapia , Colômbia , Análise Custo-Benefício , Pessoas com Deficiência/estatística & dados numéricos , Humanos , Meglumina/economia , Meglumina/uso terapêutico , Antimoniato de Meglumina , Compostos Organometálicos/economia , Compostos Organometálicos/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Resultado do TratamentoRESUMO
This study aimed to evaluate the in vivo anti-Leishmania amazonensis activity of a Phospholipase A2 (Asp49-PLA2), isolated from Bothrops jararacussu venom, encapsulated in liposomes as a modified toxin release system. The activity of the liposomes was evaluated in BALB/c mice, previously infected with 1×105 of the parasite's promastigotes. The size of the paw lesion in Asp49-PLA2-liposomal-treated animals, after 21days, was observed as decreasing by 16% relative to the untreated control group and 12% by the Glucantime®-treated animals, which was used as a reference drug. At the end of the treatment, the animals were sacrificed and the paw and lymph node tissues were collected. Part of the collection was used to recover amastigotes and another to quantify cytokines and nitrites. In the group treated with Asp49-PLA2-liposomes the parasitic load was observed to be reduced by 73.5% in the macerated lymph node, compared to the control group. Comparatively, in the paw tissue was observed a reduction of 57.1%. The infected groups treated with Asp49-PLA2-liposomes showed significant production in TNF-α measured in lymph nodes and paw (43.73pg/mL±2.25 and 81.03pg/mL±5.52, respectively) and nitrite levels (31.28µM±0.58 and 35.64µM±5.08) also measured in lymph nodes and paw tissues, respectively, compared to untreated groups. These results indicate that the Asp49-PLA2-loaded liposomes were able to activate the production of some cellular components of the protective TH1 response during the infection, constituting a promising tool for inducing the microbicidal activity of the Leishmania-infected macrophages.