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%).

Relevance of intracranial hypertension control in the management of Cryptococcus neoformans meningitis related to AIDS.

PURPOSE: To evaluate the relationship between intracranial hyperpressure (HICP) and mortality in patients with cryptococcal meningitis related to AIDS (CMRA). METHODS: This was an observational retrospective study. Patients were treated according to the Infectious Diseases Society of America recommendations during the evaluation period (days 0, 3, 5 and after hospitalization). High intracranial pressure (HICP) was defined as ICP values of C250 mm H20. The correlation between HICP and mortality at each of the three time points considered was investigated. Statistical analysis on the descriptive parameters and on the probability of a "death" event (odds ratio, OR) at each of those three time points was performed using the statistical software program Epidata. RESULTS: Eighty patients were included in this study, of whom 53 (66.25 %) were male. The average age of the patients was 37.5 ± 8.1 (range 22­55) years. The median CD4?lymphocyte cell count was 35 (range 0­367) cells/ml. Among the entire patient cohort, 53 patients had a favorable outcome, and the mortality rate was 33.75 %. At baseline (day 0), 57 subjects (71.5 %) presented HICP, and these patients had a higher mortality rate than those with a normal ICP, but the difference did not reach statistical significance[OR 1.65, 95 % confidence interval (CI) 0.56­4.84]. On day 3, 41 of the patients presented HICP, and HICP at this timepoint was significantly associated with an increased risk of mortality (OR 4.35, 95 % CI 1.56­12.09). On day 5, 35(43.5 %) patients presented HICP, and HCIP at this time point was also significantly associated with higher mortality (OR 7.23, 95 % CI 2.53­20.14). CONCLUSION: The results of this study confirm an association between HICP and mortality in patients with CMRA and indicate that the control of ICP during the first 5 days of hospitalization is more important than managing HICP only at baseline.

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.

Coccidioidomicosis / Coccidioidomicosis

La coccidiodomicosis e una micosis sistémica endémica de América, producida por los hongos dimorfos de género Coccidioides, C. immitis y C. posadasii. Estos microorganismos viven en la tierra de zonas áridas e infectan el hombre y a otras especies de animales por vía inhalatoria mediante susartroconidios. La mayor parte de las infecciones son benignas y autolimitadas debido a la eficiente respuesta de la inmunidad mediada por células. Cuando ésta falla se pueden originar diversas formas clínicas de coccidioidomicosis progresiva con un espectro que incluye, desde neumopatías crónicas hasta formas diseminadas agudas, que colocan es serio riesgo la vida de los pacientes. En las últimas décadas aumentó la incidencia de casos progresivos graves en pacientes con diversas afecciones que deterioran la inmunidad mediada por células, como el SIDA, los linfomas, la diabetes mal controlada, el empleo de corticosteroides y otras drogas inmunosupresoras y los trasplantes de órganos. El diagnóstico de esta micosis se realiza mediante la visualización o el aislamiento de los agentes causales a partir de diversas muestras clínicas, mediante estudios micológicos o histopatológicos. Las pruebas serológicas para demostrar anticuerpos específicos son también una ayuda valiosa para el reconocimientos de esta enfermedad, las más utilizadas son las inmunodifusión en gel de agar y la fijación de complemento. La anfotericina B desoxicolato, así como las formulaciones lipídicas de este antifúngico y los compuestos azólicos como el fluconazol, el itraconazol, el voriconazol y el posaconazol han demostrado ser activos frente a los hongos del género Coccidioides. En general la anfotericina B es indicada en los casos más graves esta micosis, en tanto que los compuestos azólicos son utilizados en las formas de evolución crónica, incluyendo la meningitis y como tratamiento de consolidación, una vez superado el peligro inicial. No existen hasta ahora vacuna eficaces (AU)

Coccidioidomycosis is a systemic mycosis endemic in America, produced by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. The first species is responsible for the infections in California and the second one produces coccidioidomycosis of the other endemic areas. These microorganisms live in soil of arid regions and they are able to infect human beings and other animals by inhalation of arthroconidiae. The majority of the infections are mild and self-limited due to the high efficacy of cell mediated immunity. When the immunity response is not effective, progressive coccidioidomycosis shows a wide spectrum of clinical manifestations from chronic pneumonia to acute life threatening disseminated forms. In last decades the incidence of severe disseminated coccidioidomycosis in patients with different risk factors has increased, the main associated predisposing factors are AIDS, lymphomas, diabetes, treatments with high doses of corticosteroids or other immunosuppressive drugs and organs transplantations. The diagnosis in made by finding spherules of Coccidioides in direct microscopic examination and/or the isolation of these fungi in cultures ofdifferent clinical samples, by mean of mycological or histopathological studies. Serologic tests searching for antibodies are very efficient diagnostic tools, immunodiffusion in agar gel and complement fixation test are the reactions most often used. Amphotericin B desoxycholate and its lipid formulations as well as the azolic compounds, such as fluconazole, itraconazole and second generation triazoles voriconazole and posaconazole have shown to be active against Coccidioides. Amphotericin B is usually indicated in severe cases and azoles in chronic case, fluconazole in high doses has shown to be very effective in chronic meningitis. There is not any active vaccine for the prevention of this mycosis (AU)

Histoplasmosis clásica en pacientes inmunocomprometidos / Classical histoplasmosis in the immunosupressive patient

La histoplasmosis clásica es una micosis sistémica, amplia distribución geográfica, producida por el hongo dimorfo Histoplasma capsulatum var. capsulatum.Esta micosis tiene una incidencia más elevada en América y África. El agente causal vive en las tierras ricas en sustancias orgánicas, condeyecciones de aves y murciélagos, los microconidios de la forma micelial infectan el hombre y a otras especies de animales por vía inhalatoria. Por lo general las infecciones son benignas y curan espontáneamente. Los pacientes inmunocomprometidos, como los que padecen SIDA, linfomas,infecciones por CMV, los receptores de trasplantes de órganos y los que están bajo tratamiento con altas dosis de corticosteroides u otras drogas inmunosupresoras, presentan formas progresivas y diseminadas de esta infección que suelen tener un curso fatal cuando no son tratadas. En estoscasos las lesiones se sitúan en las mucosas, la piel, los ganglios linfáticos, el hígado, el bazo, las suprarrenales y, con menor frecuencia, el SNC. El diagnóstico de la histoplasmosis se efectúa por el Hallazgo del agente causal o su aislamiento en cultivos a partir de diferentes muestras clínicas, mediante estudios micológicos e histopatológicos. Las pruebas serológicas en busca de anticuerpos, son de utilidad en el diagnóstico de los pacientes con formas de evolución crónica, las reacciones de inmunodifusión, contra inmunoelectroforesis y fijación de complemento son las más utilizadas por su especificidad. En los pacientes con formas agudas y subagudas de histoplasmosis estas reacciones no son eficaces y se debe procurara la detección de glucomananos de la (..) (AU)

Classical histoplasmosis is a systemic endemic mycosis due the dimorphic fungus Histoplasma capsulatum var capsulatum. This mycosis is prevalent in America and Africa. The etiologic agent lives in soil rich in organic materials, with birds and bat feces. The infection is acquired by inhalation of microconidiae from the mycelial form of the fungus and it is usually mild and self-limited. Patients suffering AIDS, lymphomas, CMV infections, organ transplant recipients, treatment with high dose of corticosteroids and other immunosuppressive drugs, present the disseminated progressive histoplasmosis which is usually severe and potentially fatal. In these cases lesions are located at the skin, mucous membrane, lymph nodes, liver, spleen and adrenal glands, and less frequently CNS. The diagnosis of histoplasmosis is usually made by finding this fungus in the direct microscopic examination of different clinical samples and its isolation in cultures, by mean of mycologic and histopathologic studies. Serologic tests searching for antibodies,are very useful in chronic progressive cases, immunodiffusion, counter immunoelectrophoresis and complement fixation are the more specific reactions.In acute and subacute disseminated histoplasmosis these tests are not very efficient and ELISA searching for antigens of the H. capsulatum cell wall is more often used, but it is not specific. Amphotericin B is indicated in acute cases, those with CNS involvement, patients suffering diarrhea or tuberculosis. Other cases are treated with itraconazole.There is not any active vaccine for the prevention of this mycosis (AU)

[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.

Aislamiento de Candida dubliniensis en distintos materiales clínicos: Análisis de métodos fenotípicos de diferenciación con Candida albicans / Isolation of Candida dubliniensis in different clinical samples: Analysis of phenotypical methods to differenciate from Candida albicans

Con el objeto de estimar la frecuencia de aislamientos de Candida dubliniensis en materiales clínicos en el Hospital de Infecciosas F. J. Muñiz, se identificaron 388 levaduras entre setiembre de 2005 y agosto de 2007. Doscientos doce aislamientos presentaban color verde en CHROMagar® y producían tubos germinativos y clamidoconidias en agarleche. Para diferenciar cuales de ellos correspondían a Candida albicans o a C. dubliniensis, se utilizaron distintos métodos fenotípicos y se evaluó la utilidad de cada técnica a fin de proponer un algoritmo de identificación simple, económico y confiable. Se estudió el color en 2 medios con sustratos cromogénicos, la producción de clamidoconidias en medios de Staib, agar tomate-zanahoria y agar-tabaco; en este último medio también se evaluaron las características macromorfológicas de las colonias; se evaluó la presencia de actividad lipolítica (medio-opacidad), capacidad de desarrollo a 45 °C y asimilación de D-xilosa. El 6,1% (13/212 aislamientos) correspondió a C. dubliniensis (3,3% del total de levaduras). No se pudo diferenciar entre ambas especies por el color en los medios cromogénicos usados. Las pruebas que resultaron más sensibles y específicas fueron crecimiento a 45 °C, asimilación de D-xilosa, color y desarrollo en agar-tabaco. C. albicans produjo clamidoconidias en los 3 medios diferenciales, entre 11,6% y 15,1% de los casos. La presencia de lipasas se evidenció en el 95,6% de C. albicans pero 2 de las 13 cepas de C. dubliniensis también presentaron halo de opacidad. Consideramos que se deben usar, al menos, 3 métodos diferentes para discriminar entre estas levaduras ya que ninguna prueba es absolutamente sensible o específica.

In order to estimate the frequence of Candida dubliniensis in clinical samples in F. J. Muñiz Infectious Diseases Hospital, a total of 388 yeasts from September 2005 to August 2007. There were 212 isolates which presented a green color on CHROMagar® Candida medium and produced germ tubes and chlamidoconidiae in milk-agar; so as to distinguish whether they corresponded to Candida albicans or C. dubliniensis, different phenotypical methods were utilized. It was also evaluated the usefulness of each one in order to suggest a simple, economic and reliable identification algorithm. Each isolate was subcultured in two chromogenic media and then, the following determinations were done: chlamidospores production in Staib-agar, tomato-carrot-agar and tobacco-agar, colonies macromorphology was also studied in the last medium; opacity-test in Tween 80-CaCl2 agar (lipase activity), growing capacity at 45 °C, and D-xylose assimilation. Thirteen strains (6.1%) corresponded to C. dubliniensis. The difference in color between both species on chromogenic media was not so stressed as it is pointed out in some works. The more specific and sensitive tests were the ability to grow at 45 °C, D-xylose assimilation, color and macroscopic appearance in tobacco-agar. Between 11.6% and 15.1% of C. albicans strains produced chlamidoconidiae in the 3 differential media tested. The opacity halo (lipase) was evident in 95.6% of C. albicans isolates but 2 out of 13 C. dubliniensis also presented precipitation halo. We consider that at least 3 different phenotypical methods should be used to distinguish properly these two species since none of the tests is absolutely sensitive or specific.

[Isolation of Candida dubliniensis in different clinical samples. Analysis of phenotypical methods to differentiate it from Candida albicans]. / Aislamiento de Candida dubliniensis en distintos materiales clínicos. Análisis de métodos fenotípicos de diferenciación con Candida albicans.

In order to estimate the frequence of Candida dubliniensis in clinical samples in F. J. Muñiz Infectious Diseases Hospital, a total of 388 yeasts from September 2005 to August 2007. There were 212 isolates which presented a green color on CHROMagar Candida medium and produced germ tubes and chlamidoconidiae in milk-agar; so as to distinguish whether they corresponded to Candida albicans or C. dubliniensis, different phenotypical methods were utilized. It was also evaluated the usefulness of each one in order to suggest a simple, economic and reliable identification algorithm. Each isolate was subcultured in two chromogenic media and then, the following determinations were done: chlamidospores production in Staib-agar, tomato-carrot-agar and tobacco-agar, colonies macromorphology was also studied in the last medium; opacity-test in Tween 80-CaCl2 agar (lipase activity), growing capacity at 45 degrees C, and D-xylose assimilation. Thirteen strains (6.1%) corresponded to C. dubliniensis. The difference in color between both species on chromogenic media was not so stressed as it is pointed out in some works. The more specific and sensitive tests were the ability to grow at 45 degrees C, D-xylose assimilation, color and macroscopic appearance in tobacco-agar. Between 11.6% and 15.1% of C. albicans strains produced chlamidoconidiae in the 3 differential media tested. The opacity halo (lipase) was evident in 95.6% of C. albicans isolates but 2 out of 13 C. dubliniensis also presented precipitation halo. We consider that at least 3 different phenotypical methods should be used to distinguish properly these two species since none of the tests is absolutely sensitive or specific.

[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 clÝnico, 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 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)