Trends in the molecular epidemiology and population genetics of emerging Sporothrix species.

Sporothrix (Ophiostomatales) comprises species that are pathogenic to humans and other mammals as well as environmental fungi. Developments in molecular phylogeny have changed our perceptions about the epidemiology, host-association, and virulence of Sporothrix. The classical agent of sporotrichosis, Sporothrix schenckii, now comprises several species nested in a clinical clade with S. brasiliensis, S. globosa, and S. luriei. To gain a more precise view of outbreaks dynamics, structure, and origin of genetic variation within and among populations of Sporothrix, we applied three sets of discriminatory AFLP markers (#3 EcoRI-GA/MseI-TT, #5 EcoRI-GA/MseI-AG, and #6 EcoRI-TA/MseI-AA) and mating-type analysis to a large collection of human, animal and environmental isolates spanning the major endemic areas. A total of 451 polymorphic loci were amplified in vitro from 188 samples, and revealed high polymorphism information content (PIC = 0.1765-0.2253), marker index (MI = 0.0001-0.0002), effective multiplex ratio (E = 15.1720-23.5591), resolving power (Rp = 26.1075-40.2795), discriminating power (D = 0.9766-0.9879), expected heterozygosity (H = 0.1957-0.2588), and mean heterozygosity (Havp  = 0.000007-0.000009), demonstrating the effectiveness of AFLP markers to speciate Sporothrix. Analysis using the program structure indicated three genetic clusters matching S. brasiliensis (population 1), S. schenckii (population 2), and S. globosa (population 3), with the presence of patterns of admixture amongst all populations. AMOVA revealed highly structured clusters (PhiPT = 0.458-0.484, P < 0.0001), with roughly equivalent genetic variability within (46-48 %) and between (52-54 %) populations. Heterothallism was the exclusive mating strategy, and the distributions of MAT1-1 or MAT1-2 idiomorphs were not significantly skewed (1:1 ratio) for S. schenckii (χ2 = 2.522; P = 0.1122), supporting random mating. In contrast, skewed distributions were found for S. globosa (χ2 = 9.529; P = 0.0020) with a predominance of MAT1-1 isolates, and regional differences were highlighted for S. brasiliensis with the overwhelming occurrence of MAT1-2 in Rio de Janeiro (χ2 = 14.222; P = 0.0002) and Pernambuco (χ2 = 7.364; P = 0.0067), in comparison to a higher prevalence of MAT1-1 in the Rio Grande do Sul (χ2 = 7.364; P = 0.0067). Epidemiological trends reveal the geographic expansion of cat-transmitted sporotrichosis due to S. brasiliensis via founder effect. These data support Rio de Janeiro as the centre of origin that has led to the spread of this disease to other regions in Brazil. Our ability to reconstruct the source, spread, and evolution of the ongoing outbreaks from molecular data provides high-quality information for decision-making aimed at mitigating the progression of the disease. Other uses include surveillance, rapid diagnosis, case connectivity, and guiding access to appropriate antifungal treatment.

Clinical and microbiological characteristics of paracoccidioidomycosis in patients with AIDS in Buenos Aires, Argentina.

Paracoccidioidomycosis (Pm) is a systemic disease, endemic in the American continent. There are two different clinical forms, the infant-juvenile or subacute form (PmS) and the chronic adult form (PmC). The human immunodeficiency virus (HIV) associated paracoccidioidomycosis (PmHIV) shares characteristics with both of the previously mentioned forms. The objective of this work was to describe the epidemiological, clinical and laboratory features of the PmHIV and to compare them with the ones of PmS and the PmC. A retrospective analysis of 119 patients with paracoccidioidomycosis was performed. Ninety four suffered the chronic form, 11 the subacute one and 14 were coinfected with HIV. Patients with PmHIV presented a CD4+ T lymphocytes median of 70.5 cells/µl, 71.4% had fever, 64.3% had a miliary pattern on the chest radiography, 64.3% had hepatosplenomegaly, 64.3% had mucosal lesions and 50% had skin lesions. One patient died during his hospitalization. The clinical presentation of Pm in patients with HIV resembled the subacute form with fever, hepatomegaly and skin lesions. However, they also tended to present mucosal lesions, positive serology for Pm and pulmonary parenchyma lesions as usually seen in PmC (9/14 PmHIV patients had overlapping features, while 4/14 PmHIV patients clinically resembled PmS and 1/14 PmC). The incidence of Pm has not changed with the burden of AIDS as it has happened with other fungal infections but it appears clinically different from the classic clinical forms of the disease.

Epidemiología molecular de la criptococosis en un Hospital de enfermedades infecciosas de la Ciudad de Buenos Aires: análisis de 25 años / Molecular epidemiology of cryptococcosis in an infectious diseases hospital from the city of Buenos Aires: A 25 years experience

La criptococosis es una micosis grave de distribución universal, que afecta principalmente a huéspedes inmunocomprometidos. Es una de las principales causas de morbilidad y mortalidad en los pacientes infectados con el virus de la inmunodeficiencia humana (HIV). Provoca al menos 620 000 muertes al año, representando entre el 13% al 44% de la mortalidad en pacientes HIV positivos según datos de cohortes correspondientes a países en desarrollo. (1, 2) La letalidad de la criptococosis meníngea en estudios de Argentina y Brasil muestra valores que van desde el 26% hasta el 63%. El complejo Cryptococcus neoformans/ Cryptococcus gattii, es el responsable de esta enfermedad. Existen alrededor de 70 especies pero solo dos de ellas son patógenas para el hombre: C. neoformans y C. gattii. Se reconocen 8 genotipos de este complejo, C. neoformans: VNI y VNII (C. neoformans var. grubii), VNIII (C. neoformans híbrido intervariedad AD), VNIV (C. neoformans var. neoformans) y C. gattii: genotipos VGI, VGII, VGIII y VGIV. Se han descripto híbridos interespecie VNIV/VGI, VNI/VGI, VNI/VGII. Se estudiaron 207 aislamientos de Cryptococcus, elegidos aleatoriamente, de un total de 2593 pacientes con diagnóstico de criptococosis diseminada. A los mismos se les realizó la genotipificación mediante una PCR-RFLP del gen URA5, y posterior digestión enzimática con enzimas Sau96I y HhaI. De las 207 cepas estudiadas, 174 fueron VNI (84,05%), 14 VNII (6,76%), 10 VNIII (4,83%), 2 VNIV (0,97%), 3 VGI (1,45%), 3 VGII de (1,45%) y 1 VGIII (0,49%).

Cryptococcosis is a severe worldwide mycosis, which mainly affects immunocompromised hosts and is a major cause of morbidity and mortality in HIV-infected patients. It causes 620,000 annual deaths, accounting for 13-44 % of mortality in HIV-positive individuals in developing countries. Mortality rates of meningeal cryptococcosis in studies from Argentina and Brazil go from 26 to 63 %. Cryptococcus neoformans/Cryptococcus gattii is the species complex responsible for this disease. There are about 70 species, however, only two are human pathogens: C. neoformans and C. gattii. C. neoformans genotypes are VNI and VNII (C. neoformans var. grubii), VNIII (C. neoformans intervariety hybrid AD), VNIV (C. neoformans var. neoformans). C. gattii genotypes are VGI, VGII, VGIII and VGIV. Interspecies hybrids were described: VNIV/VGI, VNI/VGI, VNI/ VGII. A total of 207 Cryptococcus isolates were randomly selected from 2593 patients with diagnosis of disseminated cryptococcosis. Genotyping was performed by PCRRFLP of UR A5 gene with restriction enzyme digestion using Sau96I and HhaI enzymes. Among the 207 studied isolates, 174 resulted VNI (84.05%), 14 VNII (6.76%), 10 VNIII (4.83%), 2 VNIV (0.97%), 3 VGI (1.45%), 3 VGII (1.45%) and 1 VGIII (0.49%).

Paracoccidioidomicosis en un hospital monovalente / PARACOCCIDIOIDIOMYCOSIS IN A SINGLE SPECIALITY HOSPITAL

La Paracoccidioidomicosis es la micosis endémica más frecuente en América latina en enfermos HIV negativos. Objetivo: analizar las características clínicas, epidemiológicas, evolución y tratamiento de los pacientes con diagnóstico de paracoccidioidomicosis asistidos en un hospital de referencia en enfermedades infecciosas en un período de 10 años. Materiales y métodos: Estudio descriptivo y retrospectivo. Se analizaron las historias clínicas de 70 pacientes con diagnóstico de paracoccidioidomicosis en el período comprendido entre Enero de 2001 y Diciembre de 2010. Resultados: se incluyeron 70 pacientes. Cincuenta y nueve presentaron la forma crónica de la enfermedad, siete la infanto-juvenil y solo cuatro resultaron positivos para el HIV. La mayoría de los enfermos fueron de nuestro país y habían nacido en Chaco y Misiones. Veintiséis eran oriundos de Paraguay. El 81,4% de los casos tuvieron compromiso pulmonar y el patrón radiológico hilio-fugal, en "alas de mariposa", fue el más frecuente. Se observaron lesiones cutáneo-mucosas en 38,57% de los enfermos. El examen directo en fresco de esputo y la escarificación de las lesiones mucocutáneas resultó ser la prueba más útil para el diagnóstico de esta micosis endémica. La serología fue positiva en el 81,3 % de los pacientes con formas crónicas y en el 42,8% de la forma infanto-juvenil. La mayoría de los enfermos fueron tratados con itraconazol; sólo dos fallecieron. Conclusión: El diagnóstico de la paracoccidioidomicosis se basa principalmente en el examen microscópico directo; los cultivos de muestras clínicas pueden fallar. La paracoccidioidomicosis debe incluirse en el diagnóstico diferencial de los pacientes que provengan de áreas endémicas y presenten compromiso de piel, mucosas o del aparato respiratorio asociado a un síndrome infeccioso inespecífico

Paracoccidioidomycosis is the most frequent endemic mycosis in Latin America in HIV negative patients. Objective: to analyze the clinical, epidemiological and treatment characteristics and the evolution of patients with diagnosis of paracoccidioidomycosis. Materials and methods: Descriptive and retrospective study. The clinical records of 70 patients with paracoccidioidomycosis were analyzed in the period between January 2001 and December 2010. Results: 70 patients were included. Fifty-nine presented the chronic form, seven had the juvenile (acute) clinical picture and only four were HIV positive. The majority of the Argentinian patients had been born in Chaco and Misiones provinces. Twenty-six were from Paraguay. 81.4% of the patients had lung involvement, the "butterfly wing" pattern was the most frequent. Muco cutaneous lessions were observed in 38.57% of the patients. Wet mount microscopy examination of sputum and mucocutaneous scarification proved to be the most useful tests for the disease diagnosis Serology tests were positive in 81.3% of patients with the chronic form and in 42.8% of those with the juvenile clinical presentation. Most of the patients were treated with itraconazole. Only two deceased. Conclusion: The diagnosis of paracoccidiodomycosis is mainly based on direct microscopic examination of clinical smears. Cultures of clinical samples may fail. Paracoccidioidomycosis should be included in the differential diagnosis of patients who come from the endemic area and present skin, mucous membranes or respiratory system compromise associated with a non-specific infectious syndrome

Historia del descubrimiento de la coccidioidomicosis / History of the discovery of the coccidioidomycosis

La coccidioidomicosis es una micosis sistémica, endémica en las zonas áridas del continente americano, producida por los hongos dimorfos Coccidioides immitis y Coccidioides posadasii. El propósito de esta presentación es dar a conocer la forma en que esta enfermedad y sus agentes causales fueron descubiertos. La enfermedad fue descubierta en 1892, en Buenos Aires, por Posadas y Wernicke. Estos investigadores describieron prolijamente las manifestaciones clínicas de la enfermedad, la histopatología, la fase tisular del agente causal y lograron reproducir la afección en animales. Este estudio fue un modelo de investigación científica para su época. Pensaron que esta nueva enfermedad era debida a un protozoario del género Psorosperma y no consiguieron cultivarlo "in vitro". En1894, Rixford y Gilchrist, en San Francisco (California), observaron un caso similar y pensaron que era debido a un protozoario, al que llamaron Coccidioides immitis. En 1900, Ophüls y Moffit, consiguieron reproducir la enfermedad en cobayos inoculados con de un moho blanquecino, cultivado a partir de las lesiones de pacientes con coccidiodomicosis y comprobaron así la naturaleza fúngica de la infección. Después de este estudio de Ophüls, los investigadoresde California demostraron la existencia de infecciones autolimitadas, la importancia de las pruebas cutáneas y serológicas con coccidioidina, la vía de infección, los tratamientos eficaces y más recientemente las características genéticas de los agentes causales.

Coccidioidomycosis is a systemic mycosis, endemic in arid regions of the American continent; it is due to the dimorphic fungi Coccidiodes immitis and Coccidiodes posadasii. The aim of this presentation is to relate the way in which this mycosis and its etiologic agents were discovered. The disease was reported for the first time in Buenos Aires in 1892, by Posadas and Wernicke. They performed a very skilful research, considered outstanding in those days. They did a very nice description of the clinical manifestations of the chronic disseminated form of coccidioidomycosis, the histopathology of skin and lymph nodes lesions, the microscopic aspects of the etiologic agent in tissues and they were able to reproduce the disease in several animal species. Posadas and Wernicke considered that this infectious disease was due to protozoa of the gender Psorosperma and they could not obtain cultures "in vitro". The first Californian patient suffering this mycosis was reported by Rixford and Gilchrist in San Francisco, in 1894. The patient was a rural worker who had come from San Joaquin Valley. They also thought that the etiologic agent was protozoa and they named this microorganism Coccidiodes immitis. In 1900, Ophüls and Moffit were able to reproduce this disease in guinea pigs by the inoculation with a white mould which had been isolated from patient's lesions. In this way they proved the fungal nature of the etiologic agent of coccidioidomycosis. After Ophüls studies the Californian researchers proved the existence of benign and self limited forms of infection, the diagnostic importance of coccidioidin skin and serologic tests, the infection portal of entry, the efficacy of different treatments and, more recently the genetic characteristics of the etiologic agents.

Brote de histoplasmosis en la Escuela de Cadetes de la Base Aérea de Morón, Provincia de Buenos Aires, República Argentina / Histoplasmosis outbreak in Morón, Buenos Aires Province, Argentina

Se describe un brote de histoplasmosis que afectó a 6 cadetes de la Fuerza Aérea Argentina, sin antecedentes patológicos previos. Todos consultaron por problemas respiratorios después de haber limpiado un hangar. En ese recinto se encontraron abundantes deyecciones de animales, presuntamente de palomas y murciélagos. Los pacientes sufrieron fiebre, mialgias, taquipnea y tos no productiva. Las radiografías y tomografías de tórax mostraron imágenes pulmonares micronodulares, engrosamiento de los tabiques interalveolares y adenopatías hiliares. Todos tuvieron una evolución favorable y no requirieron tratamiento antifúngico. Las pruebas de inmunodifusión y contrainmunoelectroforesis con antígenos de Histoplasma capsulatum fueron positivas, al igual que las intradermorreacciones con histoplasmina. Se recogieron 5 muestras de tierra del lugar, las que fueron inoculadas por vía intraperitoneal a 20 hámsteres. De los cultivos de hígado y bazo de dichos animales se consiguió aislar la fase micelial de H. capsulatum. La cepa aislada se comparó con las obtenidas de 12 pacientes argentinos utilizando perfiles genéticos y se observó un clado único con más de 96% de similitud, lo que confirma la homogeneidad de las cepas argentinas. Si bien la histoplasmosis es endémica en la Pampa húmeda, este es el primer brote totalmente documentado al sur del paralelo 34°.

An histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (> 96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

La coccidioidomicosis en Argentina, 1892-2009 / Coccidioidomycosis in Argentina, 1892-2009

Los casos clínicos de coccidioidomicosis en Argentina son pocos y han tenido lugar fundamentalmente en la extensa región árida precordillerana. Este trabajo tiene como objetivos realizar una revisión retrospectiva del total de casos de coccidioidomicosis documentados en Argentina desde el año 1892 hasta 2009 y describir una serie de casos ocurridos en los últimos 4 años. En 117 años se documentaron 128 casos. Desde la primera descripción de la enfermedad en 1892 hasta 1939 se registraron 6 casos; desde 1940 hasta 1999, 59 casos (6-14 casos cada 10 años); y los 63 casos restantes (49% del total histórico) se produjeron en el último decenio. La mediana de edad de los 34 pacientes registrados en el período 2006-2009 fue de 31 años (rango: 7-89), la relación hombre:mujer fue 1,3:1; 12 de estos individuos eran inmunocomprometidos. Veintiséis casos se confirmaron por examen microscópico, por cultivo o por ambos procedimientos; los casos restantes se confirmaron por serología. Todos los aislamientos recuperados fueron identificados como Coccidioides posadasii. Treinta pacientes residían en una amplia área geográfica con epicentro en el valle de Catamarca. Entre 2006 y 2009, la tasa de incidencia en la provincia de Catamarca se incrementó desde valores históricos inferiores a 0,5 casos cada 100 000 habitantes hasta 2,0 casos cada 100 000 habitantes. Este aumento sugiere una emergencia de la coccidioidomicosis en el área.

Clinical cases of coccidioidomycosis are rare in Argentina and are generally found in the large arid precordilleran area of the country. This study aims to perform a retrospective review of all coccidioidomycosis cases documented in the country from 1892 to 2009, and to describe those occurring in the last 4 years. One hundred and twenty eight cases were documented in the 117 year-period. Since the original description of the disease in 1892 until 1939, only 6 cases were registered; between 1940 and 1999, 59 (6-14/10 yrs) and the remaining 63 (49% of total cases) occurred in the last decade. The median age of 34 patients registered in 2006-2009 was 31 years (range: 7-89), male/female ratio was 1.3:1 and 12 patients were immunocompromised. Twenty-six cases were confirmed by direct microscopy and/or culture whereas the remaining ones by serology. All isolates were identified as Coccidioides posadasii. Thirty patients lived in a vast geographic region with epicenter in Catamarca Valley. Between 2006 and 2009, annual disease incidence rates in Catamarca Province increased from historical values below 0.5/100,000 to 2/100,000 inhabitants. Such increase suggests an emergency of coccidioidomycosis in that region.

[Histoplasmosis outbreak in Morón, Buenos Aires Province, Argentina]. / Brote de histoplasmosis en la Escuela de Cadetes de la Base Aérea de Morón, Provincia de Buenos Aires, República Argentina.

A histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (> 96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

[Coccidioidomycosis in Argentina, 1892-2009]. / La coccidioidomicosis en Argentina, 1892-2009.

Clinical cases of coccidioidomycosis are rare in Argentina and are generally found in the large arid precordilleran area of the country. This study aims to perform a retrospective review of all coccidioidomycosis cases documented in the country from 1892 to 2009, and to describe those occurring in the last 4 years. One hundred and twenty eight cases were documented in the 117 year-period. Since the original description of the disease in 1892 until 1939, only 6 cases were registered; between 1940 and 1999, 59 (6-14/10 yrs) and the remaining 63 (49% of total cases) occurred in the last decade. The median age of 34 patients registered in 2006-2009 was 31 years (range: 7-89), male/female ratio was 1.3:1 and 12 patients were immunocompromised. Twenty-six cases were confirmed by direct microscopy and/or culture whereas the remaining ones by serology. All isolates were identified as Coccidioides posadasii. Thirty patients lived in a vast geographic region with epicenter in Catamarca Valley. Between 2006 and 2009, annual disease incidence rates in Catamarca Province increased from historical values below 0.5/100,000 to 2/100,000 inhabitants. Such increase suggests an emergency of coccidioidomycosis in that region.

[Historical evolution of some clinical and epidemiological knowledge of coccidioidomycosis in the Americas]. / Evolución de los conocimientos sobre aspectos clínico-epidemiológicos de la coccidioidomycosis en las Américas.

Coccidioidomycosis is a systemic endemic mycosis caused by two dimorphic fungi of the Coccidioides genus: Coccidioides immitis and Coccidioides posadasii. This fungal infection is only endemic in the American Continent. The majority of the epidemiological, pathogenic, clinical, mycological and therapeutical findings were obtained in the U.S.A. Coccidioidomycosis was discovered in Argentina, at the end of the XIXth century by Alejandro Posadas. In the last two decades, a new endemic zone was found in the northeast of Brazil. Several countries of the region such as Mexico, Guatemala, Honduras, Venezuela and Argentina have performed epidemiological studies which allowed a better knowledge of the endemic areas and of the clinical characteristics of this mycosis.

[Clinical and microbiological study of mycetomas at the Muñiz hospital of Buenos Aires between 1989 and 2004]. / Estudio clínico y microbiológico de los micetomas observados en el hospital de infecciosas Francisco J. Muñiz en el período 1989-2004.

This work presents clinical, microbiological and outcome data collected from 76 patients with mycetomas at the Muñiz Hospital from 1989 to 2004. Forty-nine patients were male and 27 female; the mean age was 43.4 years. The majority of the patients acquired the infection in Argentina: the most affected provinces were Santiago del Estero with 31 cases, and Chaco with 11; 8 cases came from other countries (Bolivia 6 and Paraguay 2). The mean evolution of the disease was 9.2 years. The most frequently observed sites were: feet 63 cases, ankles 3, and knees 2. Forty-eight patients had bone lesions and 5, adenomegalies. The following etiological agents were identified: Madurella grisea 29 cases, Actinomadura madurae 26, Scedosporium apiospermum 5, Nocardia brasiliensis 5, Acremonium spp. 4 (Acremonium falciforme 2, Acremonium kiliense 1, Acremonium recifei 1), Madurella mycetomatis 3, Fusarium solani 2, Nocardia asteroides 1 and Streptomyces somaliensis 1. The main drugs used in the treatments were ketoconazole and itraconazole for maduromycotic mycetomas, and cotrimoxazole associated with ciprofloxacin or amikacin for actinomycetic mycetoma. Six patients had to undergo amputation, 25 cases achieved complete clinical remission and 34 showed remarkable improvement.

Estudio clínico y microbiológico de los micetomas observados en el Hospital de Infecciosas Francisco J. Muñiz en el período 1989-2004 / Clinical and microbiological study of mycetomas at the Muñiz Hospital of Buenos Aires between 1989 and 2004

Se presentan las características clínicas, microbiológicas y los resultados del tratamiento de 76 casos de micetomas observados en el período 1989-2004 en el Hospital Muñiz. Cuarenta y nueve fueron varones y 27 mujeres, con una edad promedio de 43,4 años. La mayor parte de los pacientes adquirió la infección en nuestro país, las provincias más afectadas fueron Santiago del Estero con 31 casos y el Chaco con 11; 8 enfermos procedían del exterior, 6 de Bolivia y 2 de Paraguay. El promedio de evolución de la enfermedad fue de 9,2 años. Las localizaciones más comunes fueron las de los miembros inferiores: pies 63, tobillos 3 y rodillas 2. Se comprobó compromiso óseo en 48 casos y adenomegalias en 5. Fueron identificados los siguientes agentes causales: Madurella grisea 29 casos, Actinomadura madurae 26, Scedosporium apiospermum 5, Nocardia brasiliensis 5, Acremoniun spp. 4 (Acremonium falciforme 2, Acremonium kiliense 1 y Acremonium recifei 1), Madurella mycetomatis 3, Fusarium solani 2, Nocardia asteroides y Streptomyces somaliensis 1 caso cada uno. Los tratamientos más frecuentemente utilizados fueron ketoconazol o itraconazol en los micetomas maduromicósicos y la asociación de cotrimoxazol con ciprofloxacina o amicacina en los micetomas actinomicéticos. La amputación del miembro afectado se realizó en 6 casos, 25 pacientes alcanzaron la remisión clínica completa y 34 presentaron mejorías importantes.

This work presents clinical, microbiological and outcome data collected from 76 patients with mycetomas at the Muñiz Hospital from 1989 to 2004. Forty-nine patients were male and 27 female; the mean age was 43.4 years. The majority of the patients acquired the infection in Argentina: the most affected provinces were Santiago del Estero with 31 cases, and Chaco with 11; 8 cases came from other countries (Bolivia 6 and Paraguay 2). The mean evolution of the disease was 9.2 years. The most frequently observed sites were: feet 63 cases, ankles 3, and knees 2. Forty-eight patients had bone lesions and 5, adenomegalies. The following etiological agents were identified: Madurella grisea 29 cases, Actinomadura madurae 26, Scedosporium apiospermum 5, Nocardia brasiliensis 5, Acremonium spp. 4 (Acremonium falciforme 2, Acremonium kiliense 1, Acremonium recifei 1), Madurella mycetomatis 3, Fusarium solani 2, Nocardia asteroides 1 and Streptomyces somaliensis 1. The main drugs used in the treatments were ketoconazole and itraconazole for maduromycotic mycetomas, and cotrimoxazole associated with ciprofloxacin or amikacin for actinomycetic mycetoma. Six patients had to undergo amputation, 25 cases achieved complete clinical remission and 34 showed remarkable improvement.

[Successful discontinuation of antifungal secondary prophylaxis in AIDS-related cryptococcosis]. / Interrupción exitosa de la profilaxis secundaria antifúngica en la criptococosis asociada al SIDA.

The clinical and laboratory data of 22 patients with AIDS related cryptococcosis who were able to interrupt antifungal secondary prophylaxis after HAART administration, are presented. They were 14 males and 8 females, between 15 and 50 years old (X: 34 years old). All patients presented fever and severe deterioration of their general health status, and 19 exhibited a meningeal syndrome. At the start of antifungal treatment, 59% of the cases presented < 50 CD4+ cells/microl, the median viral burden was 134,804 RNA copies/ml and the median titer of serum cryptococcal antigen was 1/3,000. Amphotericin B by intravenous route, (0.7 mg/kg/day) or fluconazole (600 to 800 mg/day) were given as a treatment of the initial episode, up to CSF cultures negativization. Oral fluconazole (200 mg/day) or intravenous amphotericin B, 50 mg twice a week, were given as a secondary prophylaxis. The secondary prophylaxis was interrupted when the patients had received HAART for an average lapse of 19 months (6 to 36 months) and the median CD4+ cell count was 249/microl. The follow up after secondary prophylaxis discontinuation lasted for a median lapse of 22 months. These data seem to show that secondary prophylaxis is not necessary when the patient are clinically asymptomatic and the CD4+ cell counts are above 150/microl.

Interrupción exitosa de la profilaxis secundaria antifúngica en la criptococosis asociada al sida / Successful discontinuation of antifungal secondary prophylaxis in AIDS-related cryptococcosis

Se presentan los datos clínicos de 22 pacientes con criptococosis asociada al VIH que interrumpieron la profilaxis antifúngica secundaria, después de haber recibido la terapéutica antirretroviral de gran actividad (TARGA). Fueron 14 varones y 8 mujeres con edades comprendidas entre los 15 y los 50 años (X: 34 años). Todos presentaron un síndrome infeccioso general grave y 19 tuvieron meningoencefalitis. En el momento del diagnóstico 59% de los enfermos tenía recuentos de células CD4+ < 50/µL,la mediana de lascargas viralesfue de 134. 804 copias ARN/ml yla mediana de los títulosde antigenemiafue de 1/3.000. El tratamiento del episodio agudo se realizó con anfotericina B por vía venosa (0,7 mg/kg/día) o fluconazol(600 a 800 mg/día), hasta la negativización de los cultivos de LCR. La profilaxis secundaria consistió en la administración oral de 200 mg diarios de fluconazoló 2 dosis semanalesde 50 mg de anfotericina B. La profilaxis secundaria antifúngica fue interrumpida cuando los enfermos habían recibido la TARGA por un lapso medio 19 meses, la mediana de los recuentos de células CD4+ fue de 249/µl. Todos estaban asintomáticos y en buen esta-do general. El lapso medio de seguimiento posterior fue de 22 meses y ningún enfermo experimentó recidivas desu micosis.

The clinical and laboratory data of 22 patients with AIDS related cryptococcosis who were able to interrupt antifungal secondary prophylaxis afterHAART administration, are presented. They were 14 males and 8 females, between 15 and 50years old (X: 34 years old). All patients presented fever andsevere deterioration of their general health status, and 19 exhibited a meningeal syndrome. At the start of antifungal treatment, 59% of the cases presented < 50 CD4+ cells/µl, the median viral burden was 134,804 RNA copies/ml and the median titer ofserum cryptococcal antigen was 1/3,000. Amphotericin B by intravenous route, (0.7 mg/kg/day) or fluconazole (600 to 800 mg/day) were given as a treatment of the initial episode, up to CSF cultures negativization. Oral fluconazole (200 mg/day) or intravenous amphotericin B, 50 mg twice a week, were given as a secondary prophylaxis. The secondary prophylaxis was interrupted when the patients had received HAART for an average lapse of 19 months (6 to 36 months) and the medianCD4+ cells counts was 249/µl. The follow up after secondary prophylaxis discontinuation lasted for a median lapse of 22 months. These data seem to show that secondary prophylaxisis not necessary when the patient are clinically asymptomatic and the CD4+ cells counts are above 150/µl.

Interrupción exitosa de la profilaxis secundaria antifúngica en la criptococosis asociada al SIDA. / [Successful discontinuation of antifungal secondary prophylaxis in AIDS-related cryptococcosis]

The clinical and laboratory data of 22 patients with AIDS related cryptococcosis who were able to interrupt antifungal secondary prophylaxis after HAART administration, are presented. They were 14 males and 8 females, between 15 and 50 years old (X: 34 years old). All patients presented fever and severe deterioration of their general health status, and 19 exhibited a meningeal syndrome. At the start of antifungal treatment, 59

of the cases presented < 50 CD4+ cells/microl, the median viral burden was 134,804 RNA copies/ml and the median titer of serum cryptococcal antigen was 1/3,000. Amphotericin B by intravenous route, (0.7 mg/kg/day) or fluconazole (600 to 800 mg/day) were given as a treatment of the initial episode, up to CSF cultures negativization. Oral fluconazole (200 mg/day) or intravenous amphotericin B, 50 mg twice a week, were given as a secondary prophylaxis. The secondary prophylaxis was interrupted when the patients had received HAART for an average lapse of 19 months (6 to 36 months) and the median CD4+ cell count was 249/microl. The follow up after secondary prophylaxis discontinuation lasted for a median lapse of 22 months. These data seem to show that secondary prophylaxis is not necessary when the patient are clinically asymptomatic and the CD4+ cell counts are above 150/microl.

[Disseminated cryptococcosis in patients with AIDS. Clinical, microbiological, and immunological analysis of 51 patients]. / Criptococosis diseminada en pacientes con SIDA. Análisis clínico, microbiológico e inmunológico de 51 pacientes.

In the context of HIV infection, cryptococcal meningitis is the most common mycosis threatening the patient's life. We conducted a retrospective evaluation to determine the epidemiological, microbiological, immunological and clinical characteristics of disseminated cryptococcosis in 51 hospitalised HIV seropositive patients. All the individuals (n = 51) presented reactive serology for HIV (ELISA and/or Western blot) and none fulfilled strict HAART treatment, previous to the opportunistic infection. CD4+ lymphocyte T counts showed levels between 361 and 0 cells/microliter (mean = 45). All patients but one had counts lower than 100 cells/microliter. Cryptococcosis presented as unique episode in 35 patients (68.6%) and in 16 as relapse (31.3%). In all of them we detected central nervous system involvement. The induction treatment was carried out with amphotericin B (AMB), continued with maintenance therapy with fluconazole. Lethality rate was 36.7%, slightly superior among patients in relapse (40%) compared to those who presented a first episode of the mycosis (35.2%). In those individuals for whom data were available, 65.2% of blood cultures, 94.1% of CSF cultures and 79.06% of microscopic CSF examination with India ink were positive. Titers of Cryptococcus neoformans capsular antigen in CSF > or = 1/1000 were found in 36.1% and > or = 1/1000 in 73.6% of serum samples. In conclusion, manifestations and severity of disseminated cryptococcosis continue maintaining the characteristics of half a decade behind, in those patients who are not treated with HAART. Neurological involvement existed in all patients of this cohort. Treatment is not able to modify the parameters of mortality seen in previous communications. Diagnostic methods applied in this study are in accordance with those in the bibliography.

Criptococosis diseminada en pacientes con SIDA. Análisis clYnico, microbiológico e inmunológico de 51 pacientes / Disseminated cryptococcosis in patients with AIDS. Clinical, microbiological, and immunological analysis of 51 patients

In the context of HIV infection, cryptococcal meningitis is the most common mycosis threatening the patients life. We conducted a retrospective evaluation to determine the epidemiological, microbiological, immunological and clinical characteristics of disseminated cryptococcosis in 51 hospitalised HIV seropositive patients. All the individuals (n = 51) presented reactive serology for HIV (ELISA and/or Western blot) and none fulfilled strict HAART treatment, previous to the opportunistic infection. CD4+ lymphocyte T counts showed levels between 361 and 0 cells/microliter (mean = 45). All patients but one had counts lower than 100 cells/microliter. Cryptococcosis presented as unique episode in 35 patients (68.6) and in 16 as relapse (31.3). In all of them we detected central nervous system involvement. The induction treatment was carried out with amphotericin B (AMB), continued with maintenance therapy with fluconazole. Lethality rate was 36.7, slightly superior among patients in relapse (40) compared to those who presented a first episode of the mycosis (35.2). In those individuals for whom data were available, 65.2 of blood cultures, 94.1 of CSF cultures and 79.06 of microscopic CSF examination with India ink were positive. Titers of Cryptococcus neoformans capsular antigen in CSF > or = 1/1000 were found in 36.1 and > or = 1/1000 in 73.6 of serum samples. In conclusion, manifestations and severity of disseminated cryptococcosis continue maintaining the characteristics of half a decade behind, in those patients who are not treated with HAART. Neurological involvement existed in all patients of this cohort. Treatment is not able to modify the parameters of mortality seen in previous communications. Diagnostic methods applied in this study are in accordance with those in the bibliography.(AU)