Optimization of Topical Therapy for Leishmania major Localized Cutaneous Leishmaniasis Using a Reliable C57BL/6 Model

When initiating the cutaneous disease named cutaneous leishmaniasis (CL), Leishmania parasites develop within the parasitophorous vacuoles of phagocytes residing in and/or recruited to the dermis, a process leading to more or less chronic dermis and epidermis-damaging inflammatory processes. Topical treatment of CL could be a mainstay in its management. Any improvements of topicals, such as new vehicles and shorter optimal contact regimes, could facilitate their use as an ambulatory treatment. Recently, WR279396, a third-generation aminoglycoside ointment, was designed with the aim to provide stability and optimal bioavailability for the molecules expected to target intracellular Leishmania. Two endpoints were expected to be reached: i) accelerated clearance of the maximal number of parasites, and ii) accelerated and stable repair processes without scars. A mouse model of CL was designed: it relies on the intradermal inoculation of luciferase-expressing Leishmania, allowing for in vivo bioluminescence imaging of the parasite load fluctuation, which can then be quantified simultaneously with the onset and resolution of clinical signs. These quantitative readout assays, deployed in real time, provide robust methods to rapidly assess efficacy of drugs/compounds i) to screen treatment modalities and ii) allow standardized comparison of different therapeutic agents

WR279,396, a Third Generation Aminoglycoside Ointment for the Treatment of Leishmania major Cutaneous Leishmaniasis: A Phase 2, Randomized, Double Blind, Placebo Controlled Study

Cutaneous leishmaniasis is due to a small parasite (Leishmania) that creates disfiguring sores, and affects more than one million persons (mainly children) each year. Treating lesions with a cream—instead of with injections as currently done—would greatly improve the well-being of affected patients. No cream formulation that would be efficient and would not create important skin irritation has been identified yet. Here, we tested a new cream formulation (WR279,396) containing paromomycin and gentamicin, two members of a well-known family of antibacterial antibiotics (aminoglycosides). Injectable paromomycin is efficient in other forms of the disease (visceral leishmaniasis). This was a carefully monitored study (phase 2) involving mainly children in Tunisia and France. The cream was applied twice a day for 20 days. The proportion of patients treated with the paromomycin-containing cream (active formulation) that cured (94%) was higher than that observed (71%) in patients treated with a cream that did not contain the active product (placebo formulation). Local irritation affected less than one-third of the patients and was usually mild. This new cream formulation was safe and effective in treating cutaneous leishmaniasis, thereby providing a new, simple, easily applicable, and inexpensive treatment for this neglected disease

Prevalence and Therapeutic Approach of Acute Pain in Emergency Provided by Triage Nursing

Prevalencia y enfoque terapéutico del dolor agudo en Urgencias brindado por la enfermería de triajePrevalência e abordagem terapêutica da dor aguda em pronto-socorro oferecidas pela enfermagem de triagemObjective: This work sought to assess the effectiveness of the treatment applied in patients with acute pain in the emergency service by triage nursing. Materials and Methods: Cross-sectional, observational descriptive study of quantitative approach, with measures of central tendency in 348 patients, conducted in 2016. An ad hoc questionnaire was used, elaborated by the emergency service, which assesses the intensity of pain through a numerical scale and a pain intervention protocol that includes physical and pharmacological measures. Results: After applying the first treatment, 80.17 % of the patients experienced improvement; 7.18 % required a second treatment and, of these, 87.5 % improved and 12.5 % suffered no modifications. The nursing staff treated the patients according to the protocol, with AINES and Metamizole, primarily. The rest were remitted to medical evaluation and another 40 patients rejected treatment. Conclusions: A high percentage of patients exist who improve their perception of pain after the first treatment administered by the triage nursing personnel. The results suggest revising and updating the protocol in the first treatment.Para citar este artículo / Para citar este artigo / To reference this articlePerera J, López F, Candelas RM, Chacón R, Morizot G. Prevalence and Therapeutic Approach of Acute Pain in Emergency Provided by Triage Nursing. Aquichan 2019; 19(4): e1944. DOI: https://doi.org/10.5294/aqui.2019.19.4.4Recibido: 08/04/2019Aceptado: 11/08/2019Online: 05/12/2019Prevalencia y enfoque terapéutico del dolor agudo en Urgencias brindado por la enfermería de triajePrevalência e abordagem terapêutica da dor aguda em pronto-socorro oferecidas pela enfermagem de triagemObjetivo: valorar la efectividad del tratamiento aplicado en pacientes con dolor agudo en el servicio de urgencias por la enfermería de triaje. Materiales y métodos: estudio descriptivo observacional, de corte transversal y de abordaje cuantitativo, con medidas de tendencia central en 348 pacientes, realizado en 2016. Se utilizó un cuestionario ad hoc, elaborado por el servicio de urgencias, que valora la intensidad del dolor mediante escala numérica y un protocolo de intervención ante el dolor que incluye medidas físicas y farmacológicas. Resultados: tras la aplicación del primer tratamiento, el 80,17 % de los pacientes experimentó mejoría; el 7,18 % requirió un segundo tratamiento y, de este, el 87,5 % mejoró y el 12,5 % no sufrió modificaciones. El personal de enfermería trató a los pacientes según el protocolo, con AINES y Metamizol, mayoritariamente. El resto fue dirigido a valoración médica y otros 40 pacientes rechazaron el tratamiento. Conclusiones: existe un alto porcentaje de pacientes que mejoran su percepción de dolor tras el primer tratamiento administrado por el personal de enfermería de triaje. Los resultados sugieren revisar y actualizar el protocolo en el primer tratamiento.Para citar este artículo / Para citar este artigo / To reference this articlePerera J, López F, Candelas RM, Chacón R, Morizot G. Prevalence and Therapeutic Approach of Acute Pain in Emergency Provided by Triage Nursing. Aquichan 2019; 19(4): e1944. DOI: https://doi.org/10.5294/aqui.2019.19.4.4Recibido: 08/04/2019Aceptado: 11/08/2019Online: 05/12/2019Prevalencia y enfoque terapéutico del dolor agudo en Urgencias brindado por la enfermería de triajePrevalência e abordagem terapêutica da dor aguda em pronto-socorro oferecidas pela enfermagem de triagemObjetivo: avaliar a efetividade do tratamento aplicado em pacientes com dor aguda no serviço de pronto-socorro pela enfermagem de triagem. Materiais e métodos: estudo descritivo observacional, de corte transversal e de abordagem quantitativa, com medidas de tendência central em 348 pacientes, realizado em 2016. Foi utilizado um questionário ad hoc, elaborado pelo serviço de pronto-socorro, que avalia a intensidade da dor mediante escala numérica, e um protocolo de intervenção ante a dor que incluiu medidas físicas e farmacológicas. Resultados: após a aplicação do primeiro tratamento, 80,17 % dos pacientes experimentaram melhora; 7,18 % necessitaram segundo tratamento e, destes, 87,5 % melhoraram e 12,5 % não sofreram alterações. A equipe de Enfermagem tratou os pacientes segundo o protocolo, com AINEs e Metamizol, predominantemente. Os demais foram dirigidos à avaliação médica, e outros 40 pacientes recusaram o tratamento. Conclusões: existe alta porcentagem de pacientes que melhoram sua percepção da dor após o primeiro tratamento receitado pela equipe de enfermagem de triagem. Os resultados sugerem revisar e atualizar o protocolo no primeiro tratamento.Para citar este artículo / Para citar este artigo / To reference this articlePerera J, López F, Candelas RM, Chacón R, Morizot G. Prevalence and Therapeutic Approach of Acute Pain in Emergency Provided by Triage Nursing. Aquichan 2019; 19(4): e1944. DOI: https://doi.org/10.5294/aqui.2019.19.4.4Recibido: 08/04/2019Aceptado: 11/08/2019Online: 05/12/201

Prevalence and Therapeutic Approach of Acute Pain in Emergency Provided by Triage Nursing

Prevalencia y enfoque terapéutico del dolor agudo en Urgencias brindado por la enfermería de triajePrevalência e abordagem terapêutica da dor aguda em pronto-socorro oferecidas pela enfermagem de triagemObjective: This work sought to assess the effectiveness of the treatment applied in patients with acute pain in the emergency service by triage nursing. Materials and Methods: Cross-sectional, observational descriptive study of quantitative approach, with measures of central tendency in 348 patients, conducted in 2016. An ad hoc questionnaire was used, elaborated by the emergency service, which assesses the intensity of pain through a numerical scale and a pain intervention protocol that includes physical and pharmacological measures. Results: After applying the first treatment, 80.17 % of the patients experienced improvement; 7.18 % required a second treatment and, of these, 87.5 % improved and 12.5 % suffered no modifications. The nursing staff treated the patients according to the protocol, with AINES and Metamizole, primarily. The rest were remitted to medical evaluation and another 40 patients rejected treatment. Conclusions: A high percentage of patients exist who improve their perception of pain after the first treatment administered by the triage nursing personnel. The results suggest revising and updating the protocol in the first treatment.Para citar este artículo / Para citar este artigo / To reference this articlePerera J, López F, Candelas RM, Chacón R, Morizot G. Prevalence and Therapeutic Approach of Acute Pain in Emergency Provided by Triage Nursing. Aquichan 2019; 19(4): e1944. DOI: https://doi.org/10.5294/aqui.2019.19.4.4Recibido: 08/04/2019Aceptado: 11/08/2019Online: 05/12/2019Prevalencia y enfoque terapéutico del dolor agudo en Urgencias brindado por la enfermería de triajePrevalência e abordagem terapêutica da dor aguda em pronto-socorro oferecidas pela enfermagem de triagemObjetivo: valorar la efectividad del tratamiento aplicado en pacientes con dolor agudo en el servicio de urgencias por la enfermería de triaje. Materiales y métodos: estudio descriptivo observacional, de corte transversal y de abordaje cuantitativo, con medidas de tendencia central en 348 pacientes, realizado en 2016. Se utilizó un cuestionario ad hoc, elaborado por el servicio de urgencias, que valora la intensidad del dolor mediante escala numérica y un protocolo de intervención ante el dolor que incluye medidas físicas y farmacológicas. Resultados: tras la aplicación del primer tratamiento, el 80,17 % de los pacientes experimentó mejoría; el 7,18 % requirió un segundo tratamiento y, de este, el 87,5 % mejoró y el 12,5 % no sufrió modificaciones. El personal de enfermería trató a los pacientes según el protocolo, con AINES y Metamizol, mayoritariamente. El resto fue dirigido a valoración médica y otros 40 pacientes rechazaron el tratamiento. Conclusiones: existe un alto porcentaje de pacientes que mejoran su percepción de dolor tras el primer tratamiento administrado por el personal de enfermería de triaje. Los resultados sugieren revisar y actualizar el protocolo en el primer tratamiento.Para citar este artículo / Para citar este artigo / To reference this articlePerera J, López F, Candelas RM, Chacón R, Morizot G. Prevalence and Therapeutic Approach of Acute Pain in Emergency Provided by Triage Nursing. Aquichan 2019; 19(4): e1944. DOI: https://doi.org/10.5294/aqui.2019.19.4.4Recibido: 08/04/2019Aceptado: 11/08/2019Online: 05/12/2019Prevalencia y enfoque terapéutico del dolor agudo en Urgencias brindado por la enfermería de triajePrevalência e abordagem terapêutica da dor aguda em pronto-socorro oferecidas pela enfermagem de triagemObjetivo: avaliar a efetividade do tratamento aplicado em pacientes com dor aguda no serviço de pronto-socorro pela enfermagem de triagem. Materiais e métodos: estudo descritivo observacional, de corte transversal e de abordagem quantitativa, com medidas de tendência central em 348 pacientes, realizado em 2016. Foi utilizado um questionário ad hoc, elaborado pelo serviço de pronto-socorro, que avalia a intensidade da dor mediante escala numérica, e um protocolo de intervenção ante a dor que incluiu medidas físicas e farmacológicas. Resultados: após a aplicação do primeiro tratamento, 80,17 % dos pacientes experimentaram melhora; 7,18 % necessitaram segundo tratamento e, destes, 87,5 % melhoraram e 12,5 % não sofreram alterações. A equipe de Enfermagem tratou os pacientes segundo o protocolo, com AINEs e Metamizol, predominantemente. Os demais foram dirigidos à avaliação médica, e outros 40 pacientes recusaram o tratamento. Conclusões: existe alta porcentagem de pacientes que melhoram sua percepção da dor após o primeiro tratamento receitado pela equipe de enfermagem de triagem. Os resultados sugerem revisar e atualizar o protocolo no primeiro tratamento.Para citar este artículo / Para citar este artigo / To reference this articlePerera J, López F, Candelas RM, Chacón R, Morizot G. Prevalence and Therapeutic Approach of Acute Pain in Emergency Provided by Triage Nursing. Aquichan 2019; 19(4): e1944. DOI: https://doi.org/10.5294/aqui.2019.19.4.4Recibido: 08/04/2019Aceptado: 11/08/2019Online: 05/12/201

Prevalência e abordagem terapêutica da dor aguda em pronto-socorro oferecidas pela enfermagem de triagem

10 páginasObjetivo: valorar la efectividad del tratamiento aplicado en pacientes con dolor agudo en el servicio de urgencias por la enfermería de triaje. Materiales y métodos: estudio descriptivo observacional, de corte transversal y de abordaje cuantitativo, con medidas de tendencia central en 348 pacientes, realizado en 2016. Se utilizó un cuestionario ad hoc, elaborado por el servicio de urgencias, que valora la intensidad del dolor mediante escala numérica y un protocolo de intervención ante el dolor que incluye medidas físicas y farmacológicas. Resultados: tras la aplicación del primer tratamiento, el 80,17 % de los pacientes experimentó mejoría; el 7,18 % requirió un segundo tratamiento y, de este, el 87,5 % mejoró y el 12,5 % no sufrió modificaciones. El personal de enfermería trató a los pacientes según el protocolo, con AINES y Metamizol, mayoritariamente. El resto fue dirigido a valoración médica y otros 40 pacientes rechazaron el tratamiento. Conclusiones: existe un alto porcentaje de pacientes que mejoran su percepción de dolor tras el primer tratamiento administrado por el personal de enfermería de triaje. Los resultados sugieren revisar y actualizar el protocolo en el primer tratamiento

Prevalencia y enfoque terapéutico del dolor agudo en urgencias brindado por la enfermería de triaje

Objective: This work sought to assess the effectiveness of the treatment applied in patients with acute pain in the emergency service by triage nursing. Materials and Methods: Cross-sectional, observational descriptive study of quantitative approach, with measures of central tendency in 348 patients, conducted in 2016. An ad hoc questionnaire was used, elaborated by the emergency service, which assesses the intensity of pain through a numerical scale and a pain intervention protocol that includes physical and pharmacological measures. Results: After applying the first treatment, 80.17 % of the patients experienced improvement; 7.18 % required a second treatment and, of these, 87.5 % improved and 12.5 % suffered no modifications. The nursing staff treated the patients according to the protocol, with AINES and Metamizole, primarily. The rest were remitted to medical evaluation and another 40 patients rejected treatment. Conclusions: A high percentage of patients exist who improve their perception of pain after the first treatment administered by the triage nursing personnel. The results suggest revising and updating the protocol in the first treatment.Objetivo: avaliar a efetividade do tratamento aplicado em pacientes com dor aguda no serviço de pronto-socorro pela enfermagem de triagem. Materiais e métodos: estudo descritivo observacional, de corte transversal e de abordagem quantitativa, com medidas de tendência central em 348 pacientes, realizado em 2016. Foi utilizado um questionário ad hoc, elaborado pelo serviço de pronto-socorro, que avalia a intensidade da dor mediante escala numérica, e um protocolo de intervenção ante a dor que incluiu medidas físicas e farmacológicas. Resultados: após a aplicação do primeiro tratamento, 80,17 % dos pacientes experimentaram melhora; 7,18 % necessitaram segundo tratamento e, destes, 87,5 % melhoraram e 12,5 % não sofreram alterações. A equipe de Enfermagem tratou os pacientes segundo o protocolo, com AINEs e Metamizol, predominantemente. Os demais foram dirigidos à avaliação médica, e outros 40 pacientes recusaram o tratamento. Conclusões: existe alta porcentagem de pacientes que melhoram sua percepção da dor após o primeiro tratamento receitado pela equipe de enfermagem de triagem. Os resultados sugerem revisar e atualizar o protocolo no primeiro tratamento.Objetivo: valorar la efectividad del tratamiento aplicado en pacientes con dolor agudo en el servicio de urgencias por la enfermería de triaje. Materiales y métodos: estudio descriptivo observacional, de corte transversal y de abordaje cuantitativo, con medidas de tendencia central en 348 pacientes, realizado en 2016. Se utilizó un cuestionario ad hoc, elaborado por el servicio de urgencias, que valora la intensidad del dolor mediante escala numérica y un protocolo de intervención ante el dolor que incluye medidas físicas y farmacológicas. Resultados: tras la aplicación del primer tratamiento, el 80,17 % de los pacientes experimentó mejoría; el 7,18 % requirió un segundo tratamiento y, de este, el 87,5 % mejoró y el 12,5 % no sufrió modificaciones. El personal de enfermería trató a los pacientes según el protocolo, con AINES y Metamizol, mayoritariamente. El resto fue dirigido a valoración médica y otros 40 pacientes rechazaron el tratamiento. Conclusiones: existe un alto porcentaje de pacientes que mejoran su percepción de dolor tras el primer tratamiento administrado por el personal de enfermería de triaje. Los resultados sugieren revisar y actualizar el protocolo en el primer tratamiento

Detection and Identification of Leishmania Species from Clinical Specimens by Using a Real-Time PCR Assay and Sequencing of the Cytochrome b Gene▿

Visceral and cutaneous leishmaniases are heterogenous entities. The Leishmania species that a given patient harbors usually cannot be determined clinically, and this identification is essential to prescribe the best species-specific therapeutic regimen. Our diagnosis procedure includes a real-time PCR assay targeted at the 18S rRNA gene, which detects all Leishmania species but which is not specific for a given Leishmania species. We developed a species identification based on sequencing of the cytochrome b (cyt b) gene directly from the DNA extracted from the clinical specimen. The sequences were analyzed using the Sequence Analysis/Seqscape v2.1 software (Applied Biosystems). This software is designed to automatically identify the closest sequences from a reference library after analysis of all known or unknown polymorphic positions. The library was built with the Leishmania cyt b gene sequences available in GenBank. Fifty-three consecutive real-time PCR-positive specimens were studied for species identification. The cyt b gene was amplified in the 53 specimens. Sequencing resulted in the identification of six different species with ≥99% identity with the reference sequences over 872 nucleotides. The identification was obtained in two working days and was in accordance with the multilocus enzyme electrophoresis identification when available. Real-time PCR followed by sequencing of the cyt b gene confirmed the diagnosis of leishmaniasis and rapidly determined the infecting species directly from the clinical specimen without the need for the isolation of parasites. This technique has the potential to significantly accelerate species-adapted therapeutic decisions regarding treatment of leishmaniasis

Traitement des leishmanioses en France : proposition d’un référentiel consensuel [Therapy of leishmaniasis in France: consensus on proposed guidelines].

International audienceBecause it relies on potentially toxic, difficult-to-handle, or expensive compounds the therapy of leishmaniasis is still a complex issue in 2010, especially for visceral leishmaniasis in immuno-suppressed subjects, or in patients with cutaneous and mucosal involvement. This induces a wide diversity of observed therapeutic practices, some being sub-optimal. The Société de Pathologie Exotique organised a meeting dedicated to the therapy of leishmaniasis in France that led to the first consensus on therapeutic guidelines. Liposomal amphotericin B is the first-line option for visceral leishmaniasis both in immunocompetent, and immunosuppressed patients (cumulated doses of 20 mg/kg and 30-40 mg/kg, respectively). Secondary prophylaxis with either liposomal amphotericin B, pentamidine or meglumine antimoniate is proposed to patients with heavy immunosuppression until immunity has been restored for at least 6 months. While the efficacy of new topical formulations of paromomycin is being tested, patients with Old World cutaneous leishmaniasis may be left untreated, or be administered a combination of superficial cryotherapy plus intralesional antimony, or even--in complex situations--receive systemic therapy. The efficacy of a short course of pentamidine (L. guyanensis/L. panamensis) and a 20-day schedule of meglumine antimoniate (L. braziliensis) is solidly established. However, in well-defined situations, local therapy of New World cutaneous leishmaniasis is now considered acceptable

C57BL/6 mice given an application of WR279396 formulation under an occlusive dressing.

<p>10⁴ luciferase-expressing <i>L. major</i> metacyclic promastigotes were inoculated into the dermis of the right ear of C57BL/6 mice (day 0). (a, b) From day eleven post-<i>L. major</i> inoculation, the topical ointment WR279396 was applied directly to parasite-loaded ears and (c) then covered with an adhesive polyurethane dressing (arrow). (d,e) Two independent leaflets of surgical tape were applied directly on the occlusive dressing. This surgical tape permitted maintenance of the dressing and kept the formulation in contact with the parasite-loaded site for two days.</p