Estudo de métodos naturais para redução de doenças fúngicas em sementes nativas da região Amazônica / Study of natural methods for reducing fungal diseases in native seeds in the Amazon region

Existe uma preocupação na produção de alimentos com a segurança sanitária desde o processo de cultivo até a sua expedição aos centros comerciais. Uma das maiores contaminações em sementes por suas características físicas e químicas, é a contaminação fúngica devida à acidez e umidade dos frutos. As doenças fúngicas entre elas, antracnose, vassoura de bruxa e podridão parda são consideradas importante doenças em pós colheita, ocorrendo, principalmente, sob condições de alta umidade relativa do ar e temperaturas elevadas (26ºC a 28ºC). Dentre as sementes da região Amazônica, destacam-se sementes de (cacau- Theobroma cacao L., pupunha- Bactris gasipaes, tucumã da Amazonas-Astrocaryum aculeatum), que apresentam problemas de contaminação fúngica durante o sistema de cultivo. Métodos de biocontroles com ação antimicrobiana: bactérias endofíticas, rizobactérias e fungo Trichoderma ssp, entre outros estão sendo estudados para a redução destas contaminações fúngicas em estudos in vitro e no campo. O objetivo deste trabalho é apresentar uma revisão bibliográfica sobre a utilização de métodos de biocontrole como uma alternativa promissora no manejo de doenças de plantas na fase de pós-colheita, com excelentes resultados em culturas de grande importância econômica. Assim novas alternativas ecologicamente sustentáveis demonstram a possibilidade de os produtos estudados serem utilizados no manejo da antracnose na pós-colheita.(AU)

There is a concern in food production with health security from cultivation process to its dispatch to redistribution centers. One of the biggest contaminations in seeds due to their physical and chemical characteristics, is the fungal contamination due to the acidity and humidity of the fruits. Fungal diseases including anthracnose, bruca's broom and brownrot are considered important diseases in post-harvest, occurring mainly under conditions of high relative humidity and high temperatures (26ºC to 28ºC). Among the seeds of the Amazon region, seeds of de (cacau- Theobroma cacao L., pupunha- Bactris gasipaes, tucumã da Amazonas- Astrocaryum aculeatum ), that present problems fungals contamination during in their growing cultures sistems. Biocontrol methods with antimicrobial action: endophytic bacteria, rhizobacteria and the fungus Trichoderma ssp, among others, are being studied to reduce these fungal contaminations in in vitro and field studies. The objective of this work is to present a bibliographic review on the use of biocontrol methods as an alternative that is promising in the management of plant diseases in the post-harvest phase, with excellent results in crops of great economic importance. Thus, new ecologically sustainable alternatives demonstrate the possibility of the studied products to be used in the management of anthracnose in the post-harvest period.(AU)

Airborne fungi in an intensive care unit / Fungos anemófilos em uma unidade de terapia intensiva

Abstract The presence of airborne fungi in Intensive Care Unit (ICUs) is associated with increased nosocomial infections. The aim of this study was the isolation and identification of airborne fungi presented in an ICU from the University Hospital of Pelotas - RS, with the attempt to know the place's environmental microbiota. 40 Petri plates with Sabouraud Dextrose Agar were exposed to an environment of an ICU, where samples were collected in strategic places during morning and afternoon periods for ten days. Seven fungi genera were identified: Penicillium spp. (15.18%), genus with the higher frequency, followed by Aspergillus spp., Cladosporium spp., Fusarium spp., Paecelomyces spp., Curvularia spp., Alternaria spp., Zygomycetes and sterile mycelium. The most predominant fungi genus were Aspergillus spp. (13.92%) in the morning and Cladosporium spp. (13.92%) in the afternoon. Due to their involvement in different diseases, the identified fungi genera can be classified as potential pathogens of inpatients. These results reinforce the need of monitoring the environmental microorganisms with high frequency and efficiently in health institutions.

Resumo A presença de fungos anemófilos nas UTIs está associada com o aumento de infecções nosocomiais. O objetivo deste estudo foi isolar e identificar quais os principais fungos anemófilos presentes em uma Unidade de Terapia Intensiva (UTI) de um Hospital Universitário de Pelotas - RS, na tentativa de conhecer a microbiota ambiental do local. Através de 40 placas de Petri com Agar Sabouraud dextrose expostas no ambiente de UTI foram coletadas amostras por exposição em locais estratégicos durante períodos da manhã e tarde por dez dias. Sete gêneros fúngicos foram identificados: Penicillium spp. (15,18%), o gênero de maior frequência, seguido de Aspergillus spp., Cladosporium spp., Fusarium spp., Paecelomyces spp., Curvularia spp., Alternaria spp., além de Zigomicetos e micélios estéreis. Houve predomínio de Aspergillus spp. (13,92%) pela manhã e Cladosporium spp. (13,92%) a tarde. Por estarem envolvidos em diferentes enfermidades, os gêneros identificados podem ser classificados como patógenos em potencial aos pacientes internados. Estes resultados reforçam a necessidade de um monitoramento dos micro-organismos ambientais com maior freqüência e eficiência nas instituições de saúde.

Osteomielitis por mucorales (OMM) asociada a artroscopia de reparación de ligamento cruzado anterior: investigación epidemiológica y recomendaciones para su prevención / Mucor osteomyelitis after arthroscopic repair of ACL. Epidemiological investigation

OBJETIVO: Describir la investigación epidemiológica de osteomielitis por Mucorales (OMM) post reparación artroscópica de LCA (RA-LCA) en Argentina. MATERIAL Y MÉTODO: 1) Revisión de los casos; 2) Relevamiento de 3 instituciones; 3) Cultivo micológico de materiales quirúrgicos; 4) Encuesta a instrumentadoras; 5) Secuenciación de las cepas de Rhizopus y 6) Redacción de recomendaciones. RESULTADOS: Del 2005 al 2017 se identificaron 40 casos de OMM (Rhizopus sp.) post reparación artroscópica de LCA en pacientes inmunocompetentes de 12 jurisdicciones de Argentina. El diagnóstico fue por cultivo (22/31), y por anatomía patológica (9). La edad promedio fue 29 años. El 84% de 38 casos eran varones. Intervinieron 13 ortopedias. El implante fue importado en 8/20 casos y nacional en 12. En las 3 instituciones se observó: manejo inadecuado del aire de quirófano, variabilidad en la limpieza del artroscopio, en el taladro utilizado, y en el manejo de materiales que llegan de las ortopedias y falta de trazabilidad de los implantes. Los cultivos micológicos de los materiales fueron negativos. La encuesta a instrumentadores confirmó los hallazgos de los relevamientos. La secuenciación de las cepas de Rhizopus demostró predominio de policlonalidad. CONCLUSIÓN: La OMM es una complicación posible luego de la RA-LCA en instituciones privadas de Argentina. No se identificó un origen único. Se detectaron múltiples prácticas que favorecen la contaminación de la cirugía con hongos filamentosos (manejo del aire de quirófano, del artroscopio, de los materiales provenientes de ortopedia, etc.). En base a estos hallazgos la Asociación Argentina de Artroscopía sugiere medidas de prevención. Implicancia clínica: Prevención de osteomielitis por Mucorales post- cirugía artroscópica para ligamento cruzado anterior. Tipo de estudio: Serie de casos. Nivel de Evidencia: IV.

OBJECTIVE: To describe the epidemiological investigation of Mucor osteomyelitis (MO) after arthroscopic repair of ACL (ARACL) in Argentina. MATERIAL Y METHODS: 1) Review of cases; 2) Survey of 3 institutions; 3) Mycological culture of surgical materials; 4) Survey of instrumentists; 5) Sequencing of Rhizopus strains and 6) Writing of recommendations. RESULTS: From 2005 to 2017, 40 cases of MO (Rhizopus sp.) Post AR-ACL were identified in immunocompetent patients from 12 jurisdictions of Argentina. The diagnosis was made by culture (22/31), and by pathology (9). The average age was 29 years. 84% of 38 cases were male. Thirteen orthopedics intervened. The implant was imported in 8/20 cases and national in 12. In the 3 institutions it was observed: inadequate handling of the operating room air, variability in the cleaning of the arthroscope, in the drill used, and in the handling of materials that come from the orthopedics and lack of traceability of the implants. The mycological cultures of the materials were negative. The survey of instrumentists confirmed the findings of the surveys. The sequencing of Rhizopus strains showed a predominance of polyclonality. CONCLUSION: MO is a possible complication after AR-ACL in private institutions in Argentina. A unique origin was not identified. Multiple practices that favor the contamination of surgery with filamentous fungi (handling of operating room air, arthroscope, materials from orthopedics, etc.) were detected. Based on these findings, the Argentine Association of Arthroscopy suggests prevention measures. Clinical relevance: Prevention of Mucor osteomyelitis after arthroscopic surgery for anterior cruciate ligament. Type study: Cases series. Level of evidence: IV.

Effects of essential oils of Rosmarinus officinalis Linn. and Origanum vulgare Linn. from different origins on Sporothrix brasiliensis and Sporothrix schenckii complex / Efeitos dos óleos essenciais de Rosmarinus officinalis Linn. e Origanum vulgare Linn. de diferentes origens em Sporothrix brasiliensis e complexo Sporothrix schenckii

Rosmarinus officinalis L. (rosemary) and Origanum vulgare L. (oregano) are known to have antimicrobial properties, but studies on sporotrichosis are scarce. This study aimed to evaluate the anti-Sporothrix spp. activity of essential oils from commercial products and oils extracted from aerial parts of these plants and analyze their chemical constituents. S. schenckii complex and S. brasiliensis (n: 25) isolated from humans, cats, dogs, and environmental soil were tested through M27-A3 guidelines of CLSI with modification for phytotherapics. The essential oils of R. officinalis L. were similar for MIC50 and MFC50 ≤2.25mg/mL for extracted oil; and 4.5mg/mL and 9mg/mL, respectively, for commercial oil. Both products showed MIC90 of 18mg/mL and MFC90 of 36mg/mL. In O. vulgare L., the extracted oil had better activity with MIC50 and MFC50 ≤2.25mg/mL, and MIC90 and MFC90 of 4.5mg/mL, whereas the commercial oil showed MIC50 and MFC50 of 9mg/mL and MIC90 18mg/mL, respectively, and MFC90 of 36mg/mL. Through gas chromatography (CG/FID), thymol and α-terpinene were majority for extracted oil of O. vulgare L., and carvacrol and γ-terpinene made up the majority of the commercial oil. Both essential oils of R. officinalis L. showed 1,8-cineole and α-pinene as major. The fungal isolates were susceptible to all tested essential oils, including in itraconazole-resistant S. brasiliensis isolates. The extracted and commercial oils of the plants presented in vitro anti-Sporothrix spp. activity, and they are promising for treatment of sporotrichosis, including in cases refractory to itraconazole. More studies should be performed about toxicity and in vivo efficacy for its safe use.(AU)

Rosmarinus officinalis L. (alecrim) e Origanum vulgare L. (orégano) são conhecidos pelas propriedades antimicrobianas, entretanto seus estudos na esporotricose são escassos. Este trabalho objetivou avaliar a atividade anti-Sporothrix spp. de óleos extraídos e comerciais dessas plantas e analisar seus constituintes químicos. Isolados do complexo S. schenckii e S. brasiliensis (n: 25) de humanos, gatos, cães e solo, foram testados pela diretriz M27-A3 do CLSI com modificações para fitoterápicos. Os óleos de R. officinalis L. foram similares com CIM50 e CFM50 ≤2.25mg/mL para extraído; e 4.5mg/mL e 9mg/mL, respectivamente, para comercial. Ambos os produtos demonstraram CIM90 de 18mg/mL e CFM90 de 36mg/mL. Em O. vulgare L., o óleo extraído apresentou melhor atividade com CIM50 e CFM50≤2.25mg/mL e CIM90 e CFM90 de 4.5mg/mL, ao passo que o óleo comercial mostrou CIM50 e CFM50 de 9mg/mL; e CIM90 de 18mg/mL e CFM90 de 36mg/mL. Por meio da cromatografia gasosa (CG/FID), timol e α-terpineno foram majoritários para o óleo extraído de O. vulgare L., e carvacrol e γ-terpineno para o comercial. Ambos os óleos de R. officinalis L. apresentaram 1,8-cineol e α-pineno como prevalentes. Os isolados foram sensíveis a todos os óleos essenciais testados, inclusive S. brasiliensis, resistentes ao itraconazol. Os óleos extraídos e comerciais de R. officinalis L. e O. vulgare L. apresentaram atividade anti-Sporothrix spp. in vitro e são promissores para o tratamento da esporotricose, inclusive em casos refratários ao itraconazol. Mais estudos devem ser realizados sobre toxicidade e eficácia in vivo para seu uso seguro.(AU)

Fungal contamination and disinfection of dental chairs, Teresina, Piauí, Brazil / Contaminação de fungos e desinfecção em cadeiras odontologicas, Teresina, Piauí, Brasil

The aim of this study was to analyze fungal contamination on dental chairs at the clinic of a Higher Education Institution in TeresinaPI, Brazil, and to evaluate the effectiveness of different disinfectants: 70% alcohol and 1% sodium hypochlorite. We selected the five sites with most contact between patient and chair: headrest, backrest, armrests, seat and foot rest. Samples were collected from these sites on 14 chairs and inoculated in agar Sabouraud culture medium containing chloramphenicol. Pathogenic fungi were isolated from all sampling sites on the chairs. Highest frequencies were found on footrest, followed in decreasing order by seat, backrest, armrests and headrest. Fourteen species of filamentous fungi were identified, belonging to the genera Alternaria, Aspergillus, Cladosporium, Curvularia, Drechslera, Fusarium, Penicillium and Paecillomyces. After sampling, seven chairs were disinfected with 70% alcohol and seven with 1% sodium hypochlorite, and samples were taken again using the same procedure. No fungal growth was detected following disinfection with sodium hypochlorite, which was clearly more effective than alcohol, after which there was still fungal growth. This study highlights the need for the biosafety protocol to include cleaning and disinfection of dental chairs with 1% sodium hypochlorite after each attendance in order to prevent crossinfection.

O objetivo deste estudo foi analisar contaminação fúngica em cadeiras odontológicas na clínica de uma Instituição de Educação Superior em TeresinaPI, Brasil, e avaliar a efetividade de diferentes desinfetantes: álcool 70% e hipoclorito de sódio 1%. Nós selecionamos os cinco locais com maior contato entre o paciente e a cadeira: encosto da cabeça, das costas, dos braços, assento e encosto dos pés. As amostras foram coletadas destes locais das 14 cadeiras e inoculadas em meio de cultura agarSabouraud contendo cloranfenicol. Fungos patogênicos foram isolados de todos os locais de amostragem das cadeiras. As frequências mais altas foram encontradas no encosto dos pés, seguido em ordem decrescente pelo assento, encosto das costas, dos braços e encosto da cabeça. Quatorze espécies de fungos filamentoso foram identificados, pertencente aos gêneros Alternaria, Aspergillus, Cladosporium, Curvularia, Drechslera, Fusarium, Penicillium e Paecillomyces. Após a coleta, sete cadeiras foram desinfe tadas com álcool 70% e sete com hipoclorito de sódio 1%, e as amostras foram colhidas novamente usando o mesmo procedimento. Não foi detectado crescimento fúngico após desinfecção com hipoclorito de sódio, que foi claramente mais efetivo que o álcool, do qual ainda houve crescimento fúngico.Este estudo destaca a necessidade da inclusão no protocolo de biossegurança a limpeza e desinfecção das cadeiras odontológicas com o hipoclorito 1% após cada atendimento, a fim de prevenir infecções cruzadas.

Caracterização da inter-relação entre as vias de sinalização Notch e TLR na paracoccidioidomicose experimental / Characterization of the inter-relationship between Notch and TLR signaling pathways in experimental paracoccidioidomycosis

A paracoccidioidomicose é uma micose sistêmica de natureza profunda que afeta preferencialmente o tecido pulmonar podendo disseminar via linfo-hematogênica para outros órgãos e tecidos, sendo causada principalmente pelo Paracoccidioides brasiliensis, fungo que apresenta dimorfismo térmico. O sistema imune inato mediado por macrófagos é extremamente importante para o controle de infecções e está envolvido na indução e regulação da resposta imune/inflamatória. Estas células são capazes de reconhecer patógenos por meio de receptores de reconhecimento de padrões (PRRs), tais como receptores Toll-like (TLR). Além desses PRRs, recentemente, demonstrou-se a importância da via de sinalização Notch no sistema imune inato e na regulação da atividade dos macrófagos. Nossos dados demonstram que a cepa Pb18 do P. brasiliensis é capaz de ativar o receptor Notch1 em macrófagos J774. A ativação desse receptor concomitante com a ativação de TLR 4 (via LPS) induz a produção de IL-6, e apresenta elevada carga fúngica e menor fagocitose, o que favorece a patogenia. Ao utilizarmos um inibidor farmacológico da γ-secretase (DAPT) para inibir a ativação do receptor Notch1 em macrófagos, é possível observar diminuição da carga fúngica, diminuição de IL-6, aumento de TNF-α e aumento da fagocitose. Entretanto, a ausência do receptor TLR 4 em macrófagos derivados de medula óssea de camundongos TLR 4-/-, na presença de DAPT, percebe-se diminuição da capacidade fagocítica desses macrófagos e também diminuição da carga fúngica, evidenciando a relação entre TLR 4 e Notch1. Em adição, realizamos um tratamento em camundongos BALB/c com DAPT previamente à infecção com Pb18. Nossos resultados evidenciaram que animais com este tratamento apresentaram diminuição da carga fúngica dos pulmões, diminuição de IL-6, ativação de macrófagos e aumento de IgG, após 45 dias de infecção, indicando um perfil de cura desses animais. O mesmo tratamento foi realizado em camundongos BALB/c NUDE, seguido da infecção com Pb18. Nestes animais, verificamos que há maior produção de citocinas pró-inflamatórias no pulmão, aumento de células CD19+ e a carga fúngica dos animais tratados manteve-se similar ao dos animais não tratados, indicando que o perfil protetor observado em animais com DAPT é dependente da resposta das células T. Juntos, esses resultados evidenciam que o Pb18 é capaz de ativar o receptor Notch1 em macrófagos e utiliza a via de sinalização Notch-TLR 4 como um possível mecanismo de escape, podendo fornecer uma nova abordagem de estudo da imunidade envolvida na paracoccidioidomicose experimental

Paracoccidioidomycosis is a systemic mycosis of deep nature that primarily affects the lung and can spread via lymphatic and hematogenous to other organs and tissues. It is mainly caused by Paracoccidioides brasiliensis fungus which exhibit thermal dimorphism. The innate immune system mediated by macrophages is extremely important for the control of infection and is involved in the induction and regulation of immune/inflammatory response. These cells are able to recognize pathogens through pattern recognition receptors (PRRs) such as Toll-like receptors (TLR). Beyond these PRRs, the importance of Notch signaling has recently been demonstrated in the innate immune system and the regulation of macrophage activity. Our data demonstrate that the Pb18 strain of P. brasiliensis is able to activate the Notch1 receptor in J774 macrophages. Activation of this receptor with also activation of TLR 4 (via LPS) induces IL-6 production, induces phagocytosis and decreases fungal burden, which favors the pathogenesis. By using a γ-secretase pharmacological inhibitor (DAPT) for inhibiting the activation of Notch1 receptor on macrophages, it is possible to observe decreased fungal burden, less production of IL-6, and increased TNF-α and phagocytosis. However, due to the absence of TLR 4 receptor in bone marrow derived macrophages from TLR 4-/- mice, these macrophages showed decreased phagocytic ability and also reduced fungal burden in the presence of DAPT, showing a relationship between TLR 4 and Notch1. In addition, we made a treatment with DAPT in BALB/c mice prior to infection with Pb18. And our results showed that DAPT-treated animals exhibited a decrease of fungal burden in the lungs, and a decrease of IL-6. Furthermore, we observed an increase of IgG after 45 days of infection, indicating probably a healing of these animals. Same treatment was made in BALB/c NUDE mice, followed by infection with Pb18. In these animals, we observed an increased production of proinflammatory cytokines in the lung and increased CD19+ cells, but fungal burden was similar in both group (treated and untreated), which indicates that treatment with DAPT is dependent on T cell response. Taken together, these results showed that Pb18 is able to activate the Notch 1 receptor on macrophages and uses the Notch-TLR 4 signaling pathway as a possible escape mechanism, and may provide a new immunity study approach in experimental paracoccidioidomycosis

New insights on the development of fungal vaccines: from immunity to recent challenges

Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality.

Preliminary Study on Some Actinomycetes and Evaluation of Their Potential Antagonism against Fungal Pathogens.

Aims: Control of microbial pathogens by using antagonistic microorganisms is a promising alternative to chemical fungicides. The objective of the present study was to isolate and characterize soil actinomycetes and to their inhibitory activity against some fungal plant pathogens. Place and Duration of Study: National Park “El Chico”, Hidalgo State, and Laboratory of the Southeast Unit of CIATEJ, Yucatán, México, between June 2010 and May 2011. Methodology: Actinomycete species were isolated from six composite soil samples using microbiological standard procedures. All isolates were phenotypically characterized. Antagonistic isolates were selected according to the inhibitory growing of Fusarium sp. and Candida albicans. Afterwards, a new evaluation for the isolates selected was done against Helminthosporium sp., Curvularia sp., and Aspergillus niger. Actinomycetes were identified performing an analysis of the 16S rDNA gene sequence. Results: 164 actinomycete strains were characterized by morphological and biochemical features. Six of them, inhibited the growth of Fusarium sp. and C. albicans from 5 to 10 mm distance in between the actinomycete´s colony growth border of fungal or yeast. A growing reduction from 50 to 83 % in the in vitro antagonism assays was observed for Helminthosporium sp., Curvularia sp., and Aspergillus niger. Results in disc diffusion assays suggested an inhibitory growing capacity of CACIA-1.46HGO for P. capsici, this behavior could be due to the production of diffusible compounds related to secondary metabolism, hydrolytic enzymes, or both of them. Four antagonistic isolates were identified into Streptomyces genus and one as Microbacterium sp. through 16S rDNA gene sequence. Conclusion: Actinomycetes could be potentially a control tool to prevent several fungal commercial plants diseases. However, in situ isolate evaluations are suggested to be investigated.

Profilaxis antifúngica en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against fungal infections in solid organ and hematopoietic stem cells transplantation

Invasive fungal infections are an important cause of morbidity and mortality in SOT and HSCT recipients. The main species involved are Candida spp. and Aspergillus spp, less frequently Cryptococcus spp., causal agents of mucormycosis and Fusarium spp. Usually occur within the first six months post-transplant, but they do it later, especially during episodes of rejection, which maintains the state of immune system involvement. Prophylaxis recommendations are specific to each type of transplant. In liver transplantation use of fluconazole is recommended only in selected cases by high risk factor for invasive fungal infections (A1). If the patient has a high risk of aspergillosis, there are some suggestions for adults population to use amphotericin B-deoxycholate, liposomal amphotericin B or caspofungin (C2) without being validated none of these recommendations in pediatric population. In adult lung transplant patients where the risk of aspergillosis is higher than in other locations, we recommend universal prophylaxis with itraconazole 200 mg/day, nebulised liposomal amphotericin B or voriconazole (C2), no validated recommendations for pediatrics. In HSCT, universal prophylaxis is recommended only in allogeneic and autologous selected cases. The most accepted indication is fluconazole (A1), and posaconazole (A1) or micafungin (A1) in selected cases with high risk of aspergillosis.

Las infecciones fúngicas invasoras constituyen una importante causa de morbilidad y mortalidad en los pacientes receptores de TOS y TPH. Los principales agentes involucrados son Candida spp. y Aspergillus spp, menos frecuentemente Cryptococcus spp., agentes causales de mucormicosis y Fusarium spp. Se presentan habitualmente dentro de los primeros seis meses posttrasplante, pero también lo hacen en forma más tardía, especialmente durante episodios de rechazo, en que se mantiene el estado de compromiso del sistema inmune. Existen recomendaciones de proilaxis especíicas para cada tipo de trasplante. En trasplante hepático se recomienda el uso de fluconazol sólo en casos seleccionados por factores de riesgo (A1). Si existe riesgo de asper-gilosis, hay algunas sugerencias en adultos para el uso de anfotericina B-deoxicolato, anfotericina liposomal o caspofungina (todo en categoría C2), sin estar validada ninguna de estas recomendaciones en pediatría. En trasplante pulmonar en paciente adulto, donde el riesgo de aspergilosis es superior a otras localizaciones, se recomienda proilaxis universal, con itraconazol 200 mg/día, anfotericina liposomal nebulizada o voriconazol (C2), sin recomendaciones validadas para pediatría. En TPH, se recomienda proilaxis universal en trasplante alogénico y sólo para casos seleccionados en trasplantes autólogos. La indicación más aceptada es fluconazol (A1), siendo alternativas a evaluar dependiendo del riesgo de aspergilosis, posaconazol (A1) y micafungina (A1).

Antifungigrama para comprovar o potencial de ação dos extratos vegetais hidroglicólicos sobre Candida sp. (Berkhout) / Etest to confirm the action potential of plant hydroglycol extracts on Candida sp. (Berkhout)

A candidíase vaginal é uma doença causada, na maioria das vezes, pelo fungo do gênero Candida sp, que habita o trato gastrintestinal e geniturinário da espécie humana e pode tornar-se patogênico sob determinadas condições. A maioria dos indivíduos desenvolve defesas imunológicas que impedem a proliferação e desenvolvimento de candidíase localizada ou disseminada. Embora a causa exata do aumento de espécies não-albicans seja desconhecida, há evidências de que a própria terapia antifúngica possa estar contribuindo para o processo. Linhagens de C. glabrata são mais resistentes aos imidazólicos do que a C. albicans, sendo necessária uma concentração 10 vezes superior de miconazol para eliminar a C. glabrata quando comparada a C. albicans. Foi realizado um antifungigrama testando o potencial de ação de produtos vegetais sobre o fungo Candida sp. Foi observado que, ocorreu inibição do fungo no contato com os extratos hidroglicólicos das plantas Arctium lappa L., Calendula officinalis L., Stryphnodendron adstringens (Mart.) Coville e Tabebuia avellanedae Lorentz ex Griseb. A importância deste trabalho reside na possibilidade de desenvolvimento de tratamento complementar, menos agressivo, de menor custo e sem toxidade, o que possibilitaria melhor qualidade de vida para portadoras de candidíase vaginal recorrente ou não.

Vaginal candidiasis is a disease caused, in most cases, by the fungus of the genus Candida sp., which inhabits the gastrointestinal and genitourinary tracts of the human species and can become pathogenic under certain conditions. Most individuals develop immune defenses that prevent the proliferation and the development of localized or disseminated candidiasis. Although the exact cause of the increase in non-albicans species is unknown, there is evidence that antifungal therapy itself may have contributed to it. Strains of C. glabrata are more resistant to imidazole than C. albicans, and a 10-fold higher concentration of miconazole is required to eliminate C. glabrata compared to C. albicans. Etest was performed by testing the action potential of plant products on the fungus Candida sp. Inhibition of the fungus occurred when it was in contact with the hydroglycol extracts of plants Arctium lappa L., Calendula officinalis L., Stryphnodendron adstringens (Mart.) Coville and Tabebuia avellanedae Lorentz ex Griseb. The importance of this study lies in the possibility of developing a complementary treatment, less aggressive, of lower cost and without toxicity, which would allow better life quality for women with vaginal candidiases that are recurrent or not.

Colonización de especies de malassezia en piel sana de niños en edad preescolar / Colonization of malassezia species on healthy skin of preschool children

Las levaduras del género Malassezia forman parte de la piel normal del hombre y otros vertebrados. La reciente descripción de nuevas especies para el género ha incentivado interés en el estudio de las mismas en diversos países, por lo tanto, es importante realizar investigaciones tendentes a obtener datos epidemiológicos de las especies en países tropicales como Venezuela. El estudio se realizó en piel sana de niños en edad preescolar (2 a 7 años) Las muestras fueron tomadas de diferentes áreas del cuerpo e inoculadas en el medio modificado de Dixon y Sabouraud Dextrosa Agar e incubadas a 32 °C. La identificación de las especies se realizó siguiendo las claves descritas por Guého y col. En la población estudiada se aislaron tres especies M. furfur, M. globosa y M. slooffiae. La especie predominante fue M. furfur con un 76,2% en todos los grupos etareos, seguida de M. globosa 16,7% y M. slooffiae 7,1% En relación a las localizaciones anatómicas M. furfur presentó un predominio en espalda (31,2%) seguida de pabellón auricular y pecho (21,9% respectivamente). M. globosa se aisló con mayor frecuencia de cuero cabelludo (71,4%) y M. slooffiae se observó en espalda (66,7%) y pabellón auricular (33,3%). Según las pruebas estadísticas aplicadas, no se encontraron diferencias significativas entre los grupos evaluados. Cabe destacar la importancia de continuar las investigaciones en otros grupos etarios, para establecer cuáles son las especies prevalentes en nuestra región y evaluar su potencial patógeno

Malassezia yeast forms part of the normal skin on man and other vertebrates. Recent descriptions of new species have stimulated interest in their study in diverse countries; it is important to conduct further research to collect epidemiological data about the species in tropical countries such as Venezuela. This study was made on healthy skins of preschool-age children (2 to 7 years). Samples were taken from different areas of the body, inoculated into a modified medium of Dixon and Sabouraud Agar and incubated at 32°C. Species identification was made following the code described by Guého and collaborators. In the population of children, three species were isolated: M furfur, M. globosa and M. slooffiae. The predominant species was M. furfur with 76.2% in all ages studied, followed by M globosa, 16.7%, and M. slooffiae, 7.1%. In relation to anatomical locations, M. furfur predominated on the back (31.2%), followed by the auricle (outer ear) and chest (21.9%), respectively. M globosa was most frequently isolated from the scalp (71.4%) and M. slooffiae was observed on the back (66.7%) and the auricle (33.3%). According to the statistical tests applied, there were no significant differences between the evaluated groups. It is important to continue this research with other age groups, to establish the prevalent species in this region and evaluate their pathogenic potential

Resultados de profilaxis con itraconazol 800 mg/día vía oral en adultos con leucemia aguda y neutropenia de alto riesgo: Hospital del Salvador 2006-2008 / Itraconazole 800 mg for the prophylaxis of fungal infections in patients with acute leukemia and severe neutropenia

Background: Systemic fungal infections and specifically invasive aspergillosis (IA) are associated with a high morbi-mortality rate in patients with hematologic malignancies. Itraconazole kinetic studies show that plasma levels are not satisfactory, even though there is a reduction of the severity in clinical cases. Aim: To evaluate the results of oral prophylaxis with high dose itraconazole, 400 mg bid, among patients with adult acute leukemia. Material and Methods: Prospective analysis of 93 high risk febrile episodes (with an absolute neutrophil count of less than 500 x mm3 for more 10 days), that occurred in 76 patients. Results: Seventy five percent of episodes occurred in patients with acute myeloid leukemia and 25 percent in patients with acute lymphoblastic leukemia. Fifty two percent occurred during the induction of chemotherapy. Median duration of severe neutropenia was 21 days (range 10-48). Median duration of itraconazole prophylaxis was 17 days (range 6-34). A low frequency of invasive fungal infections was observed (17 percent). According to diagnostic criteria, 5 percent of episodes corresponded to persistent fever , 1 percent and 11 percent of episodes, to probable or possible IA, respectively. No confirmed or proven IA was observed. Mortality of IA was 18 percent. No serious adverse events due to itraconazole were observed. Conclusions: The use of high dose itraconazole prophylaxis in adult patients with acute leukemia and severe neutropenia was associated to low incidence and mortality of invasive mycoses.

Efficacy of Itraconazole Prophylaxis for Autologous Stem Cell Transplantation in Children with High-Risk Solid Tumors: A Prospective Double-Blind Randomized Study

PURPOSE: The risk of invasive fungal infection is greater for allogeneic hematopoietic stem cell transplantation (HSCT) than for autologous transplantation. Therefore, many transplantation centers use antifungal prophylaxis for allogeneic HSCT, however, there exists no standard guidelines or consensus regarding autologous HSCT. MATERIALS AND METHODS: A prospective double-blind randomized study was conducted in autologous HSCT recipients who were divided into prophylaxis and empirical treatment groups, and we investigated the efficacy of itraconazole prophylaxis in pediatric autologous HSCT. RESULTS: Total 87 autologous HSCT episodes in 55 children with high-risk solid tumors were studied. No invasive fungal infections occurred in either group. However, patients in the prophylaxis group had a significantly shorter duration of fever (p < 0.05) and received antibacterial treatment of shorter duration (p < 0.05) with fewer numbers of antibiotics (p < 0.05 for the use of second line antibiotics) than those in the empirical group. No significant additional adverse events were found with itraconazole prophylaxis. CONCLUSION: Although beneficial effects such as a shorter duration of fever and reduced need for antibiotic use were observed in the prophylaxis group, the results were not sufficient to draw a definite recommendation about the routine use of antifungal prophylaxis in pediatric autologous HSCT recipients with high-risk solid tumors (Trial registration: NCT00336531).

Distribution of filamentous fungi causing invasive fungal disease at the haematological unit, Hospital de Clínicas de Porto Alegre, Brazil

Very limited data are available in the literature to elucidate the aetiology of invasive mould infections in Latin America. Here we report that Aspergillus species caused only half of such cases in a cohort study conducted over 21 months in a university hospital in Porto Alegre, Southern Brazil. Fusarium spp. were the second most prevalent moulds (20.7 percent), followed by Zygomycetes (13.8 percent). The importance of obtaining local epidemiological data for adequately guiding empirical antifungal therapy is reinforced.

Once-weekly liposomal amphotericin B for prophylaxis of invasive fungal infection after graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: a comparative retrospective single-center study

The liposomal formulation of amphotericin B [LAmB] has been shown to cause few and mild infusion-related reactions, while achieving high plasma and tissue concentrations compared with conventional amphotericin B. We investigated the efficacy and safety of high-dose LAmB [7.5 mg/kg once weekly] prophylaxis of fungal infections in allogeneic stem-cell transplanted [allo-SCT] patients with graft-versus-host disease [GvHD]. Retrospective, comparative, single-center. Forty-two patients receiving high-dose prednisone for GvHD after allo-SCT had LAmB prophylaxis; 83 patients in the control group received other antifungal prophylaxis. In the LAmB prophylaxis group, the median duration of treatment was 7 weeks. The cumulative incidence of invasive fungal infection was 8% at 1 year after transplantation, 8% at 2 years and 16% at 3 years in the LAmB group vs. 36% at 1 year, 44% at 2 years and 49% at 3 years in the other prophylaxis group [P=.008]. Fungal infection-related mortality after transplantation was observed in none of the patients in the LAmB prophylaxis group vs. 12 patients [14%] at 1 year, 14 patients [17%] at 2 years and 16 patients [19%] at 3 years in the control group [P = .005]. The tolerance of the treatment was good with only 5 patients [12%] having a reversible nephrotoxicity leading to temporary treatment discontinuation. High-dose LAmB prophylaxis seems effective and well tolerated in this short series of allo-SCT patients with GvHD. Prospective clinical studies are required to confirm these results

Colonización por levaduras en piel sana de recien nacidos / Yeast colonization on healthy skin in newborns

En el niño recién nacido la colonización por especies de levaduras puede ser el precursor de una infección clínica. En esta investigación se evaluó la colonización por levaduras en piel de neonatos nacidos a término en las primeras 48 horas del nacimiento. Las muestras de piel, de 100 niños, se tomaron de diferentes regiones anatómicas. Se empleó el método de la impronta con cinta plástica transparente. Se realizó un examen directo con azul de metileno (0,25 por ciento) y se cultivó en los medios Sabouraud Dextrosa Agar y Dixon con antibióticos. La identificación de los aislados se hizo según metodología clásica. Los resultados indican que los neonatos presentaron una colonización por levaduras en un 45 por ciento. Se observó una colonización baja por Malassezia furfur (5 por ciento) y el predominio de Candida parapsilosis (87,9 por ciento). Esta especie de Candida fue aislada en un 54,2 por ciento cuando el nacimiento fue por cesárea y, 33,7 por ciento cuando fue por parto. El alto porcentaje de colonización por C. parapsilosis tanto en los niños nacidos por parto como por cesárea podría deberse a la trasmisión horizontal a partir de las manos del personal de salud que los atiende

In the newborn, colonization by yeast species may be the precursor for a clinical infection. This study assessed yeast colonization on the skin of term infants during the first 48 hours after birth. Skin samples of 100 children were taken from different anatomical regions. The stamp method with transparent plastic tape was used. A direct test with methylene blue (0.25 percent) was made and cultured in Sabouraud dextrose agar and Dixon media with antibiotics. Isolates were identified according to classic methodology. Results indicate that 45 percent of the newborns had yeast colonies. Low colonization by Malassezia furfur (5 percent) and the predominance of Candida parapsilosis (87.9 percent) were observed. This species of Candida was isolated in 54.2 percent of births by caesarean section and 33.7 percent of natural births. The high rate of colonization by C. parapsilosis in children born by caesarean as well as normal delivery could be due to horizontal transmission from the hands of health workers taking care of them

Estudio clínico doble ciego controlado para evaluar la respuesta terapéutica con terbinafina HCL 1 por ciento Panacap crema sin aceite comparado a crema placebo en el tratamiento de onicomicosis subungueal distal causada por T. rubrum en el lecho de la uña del primer dedo / Study clinical blind double controlled to evaluate the therapeutic answer with terbinafina HCL 1 percent Panacap it cremates without oil compared to cream placebo in the treatment of onicomicosis subungueal distal caused by T. rubrum in the channel o

Este es un estudio clínico piloto (experimental), doble ciego controlado para evaluar la respuesta terapeutica de terbinafina HCI 1 por ciento Panacap crema sin aceite en comparación con crema de placebo en el tratamiento de Onimicosis (OSD) por Tricophyton rubrum en el lecho de la uña del primer dedo. Este estudio se llevó a cabo en el Centro Nacional de Dermatología "Francisco José Gómez Urcuyo" con 11 pacientes.