Resumen Introducción : La histoplasmosis es una micosis sis témica de distribución universal, altamente endémica en las Américas. Es causada por un hongo dimórfico: Histoplasma capsulatum var. capsulatum. Afecta tanto a inmunocompetentes como a inmunocomprometidos, se observan formas progresivas y diseminadas. Un factor de riesgo muy importante es la infección por HIV/sida, con una tasa de mortalidad del 20-40% en América Latina. El diagnóstico de esta micosis se realiza por métodos convencionales y moleculares o por detección de antígenos y anticuerpos. Métodos : En este estudio retrospectivo, longitudinal y analítico, realizado en un periodo de 2 años, se evaluó la sensibilidad (S) y especificidad (E) de un kit comercial para la detección de antígeno de Histoplasma por técnica de EIA (HC-Ag) en 50 pacientes con histoplasmosis aso ciada a sida. Además, se comparó su rendimiento con el de otras técnicas diagnósticas utilizadas habitualmente en nuestro laboratorio. Resultados : HC-Ag tuvo una S del 94%, E del 96%, coeficiente de verosimilitud positiva (CVP) de 20.68 y coeficiente de verosimilitud negativa (CVN) de 0.06. El tiempo de demora de los resultados fue de 4 días, simi lar al de la detección de anticuerpos y n-PCR y mucho menor que el de los hemocultivos. La combinación de métodos mejoró la S a 100%; con valores similares en E. Conclusión : El método HC-Ag demostró su utilidad en el diagnóstico de histoplasmosis diseminada progresiva y la combinación de métodos es una buena opción para aumentar la sensibilidad y disminuir el tiempo para llegar al diagnóstico de certeza. Esto permite mejorar la estrategia en el manejo de la enfermedad y reducir su tasa de letalidad.

Abstract Introduction : Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. Methods : In this retrospective, longitudinal and ana lytical study, carried out over a period of 2 years, the sensitivity (S) and specificity (E) of a commercial kit for the detection of Histoplasma antigen by EIA technique (HC-Ag) was evaluated in 50 patients with AIDS-associated histoplasmosis. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. Results : HC-Ag had a S of 94%, E 96%, positive likeli hood coefficient (CVP): 20.68 and negative likelihood coefficient (CVN): 0.06. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S to 100%; with simi lar values in E. Conclusion : The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improv ing the strategy in the management of the disease and decreasing its case-fatality rate.

Background: Histoplasmosis is a mycosis with a high prevalence in HIV/AIDS patients. Clinical presentation includes a wide spectrum of manifestations and diagnosis usually takes up to several weeks in patients who do not present cutaneous lesions. Aim: To determine the clinical and microbiological characteristics as well as some biochemical parameters in patients with AIDS-associated histoplasmosis without tegumentary lesions, in order to develop a guideline which enables an early empiric treatment in cases of difficult diagnosis. Methods: Medical records of 86 patients with histoplasmosis were reviewed; 31 patients with diagnosis of AIDS-associated histoplasmosis without cutaneous lesions were analyzed. Results: Fever was the most frequent symptom (96.7%), lung involvement was observed in 22 patients (70.9%), the most commonly radiological pattern was miliary pattern [(12/22), 54.5%]. Nineteen patients presented with splenomegaly. Blood culture sensitivity was 93.3% (28/30) and serology was positive only in 23.5% of the cases. Eight patients died (25.8%). Patients in which CD4+ T cell lymphocytes count was < 50 cells/μl, albumin levels < 2.5 g/dl and who presented with pancytopenia had an unfavorable outcome. Conclusions: In HIV seropositive patients with fever associated to splenomegaly and bilateral miliar pattern in chest radiography, the empiric treatment with amphotericin B must be considered if signs and symptoms of unfavorable outcome are present and due to the time that it takes to arrive at an accurate diagnosis. In order to confirm the diagnosis, all microbiological samples should be collected prior to initiating therapy.

Resumen Antecedentes: La histoplasmosis es una micosis de gran relevancia en pacientes con SIDA. El cuadro clínico puede ser muy variado y, en enfermos que no desarrollan lesiones cutáneas, el diagnóstico suele demorar varias semanas. Objetivo: Establecer pautas que permitan emplear un tratamiento empírico y precoz en pacientes con histoplasmosis asociada al SIDA sin manifestaciones tegumentarias y determinar las características clínicas, microbiológicas y algunos parámetros bioquímicos en los casos de difícil diagnóstico. Métodos: Se analizaron las historias clínicas de 86 pacientes con histoplasmosis. Fueron seleccionados 31 enfermos con histoplasmosis asociada con SIDA sin lesiones cutáneas. Resultados: La fiebre fue el síntoma más frecuente (96,7%), el compromiso pulmonar se comprobó en 22 enfermos (70,9%). El patrón radiológico más frecuentemente hallado en las radiografías de tórax fue el miliar o micronodulillar bilateral [(12/22), 54,5%]. Diecinueve enfermos presentaron esplenomegalia. Los hemocultivos demostraron una sensibilidad de 93,3% (28/30) y la serología fue positiva en 23,5% de los casos. Fallecieron ocho pacientes (25,8%). Los pacientes con recuentos de linfocitos T CD4+ menores a 50 céls/μl, albúmina menor a 2,5 g/dl y pancitopenia evidenciaron un pronóstico desfavorable. Conclusiones: En los pacientes con infección por VIH, fiebre asociada a esplenomegalia y lesiones micronodulillares bilaterales en la radiografía de tórax debe considerarse el tratamiento empírico con anfotericina B cuando existan signos o síntomas de mal pronóstico, debido al tiempo de demora hasta el diagnóstico definitivo. Previo a iniciar el tratamiento deben tomarse todas las muestras para los estudios microbiológicos que permitan confirmar luego la presunción diagnóstica.

Cerebral aspergillosis is a rare disease with high mortality rates in AIDS patients. It is important to take this into account in the differential diagnosis of a brain expansive lesion. A high level of suspicion is required to make an early diagnosis. We present a case of an HIV-infected patient with progresive neurological disease caused by Aspergillus flavi. We review 40 previously published cases of central nervous system aspergillosis in patients with AIDS.

Resumen La aspergilosis cerebral es una patología infrecuente, pero de elevada mortalidad en pacientes con SIDA. Es importante considerarla entre los diagnósticos diferenciales ante una lesión expansiva cerebral. Se requiere un alto grado de sospecha para poder realizar un diagnóstico precoz. Se presenta el caso de un paciente con infección por VIH con un cuadro neurológico rápidamente progresivo por Aspergillus sección flavi. Se realiza una revisión de 40 casos publicados de aspergilosis cerebral en pacientes con SIDA.

Neurohistoplasmosis is a rare disease, most prevalent in immunosuppressed patients, secondary to disseminated disease with a high mortality rate when diagnosis and treatment are delayed. We report a previously healthy 12 year old girl, from a bat infested region of Tucuman Province, Argentine Republic, who developed meningoencephalitis due to Histoplasma capsulatum. Eighteen months prior to admission the patient started with headaches and intermittent fever. The images of the central nervous system showed meningoencephalitis suggestive of tuberculosis. She received antibiotics and tuberculostatic medications without improvement. Liposomal amphotericin B was administered for six weeks. The patient's clinical status improved remarkably. Finally the culture of cerebral spinal fluid was positive for micelial form of Histoplasma capsulatum. The difficulties surrounding the diagnosis and treatment of neurohistoplasmosis in immunocompetent patients are discussed in this manuscript, as it also intends to alert to the presence of a strain of Histoplasma capsulatum with affinity for the central nervous system.

La histoplasmosis en el sistema nervioso central es una enfermedad poco frecuente, con mayor prevalencia en pacientes inmunosuprimidos, secundaria a enfermedad diseminada (5%-10%), con una alta tasa de mortalidad en caso de demorarse el diagnóstico y su tratamiento. Presentamos a una niña de 12 años previamente sana, que desarrolló meningoencefalitis por Histoplasma capsulatum sin evidencia de enfermedad generalizada. La paciente era oriunda de una región infestada por murciélagos de Tucumán, República Argentina, y desarrolló, durante 18 meses previos a su internación, cefalea y síndrome febril. Las imágenes del sistema nervioso central mostraron meningoencefalitis, que sugirió tuberculosis. Recibió tratamiento antibiótico y tuberculostático, sin mejoría. Luego recibió anfotericina B liposomal durante 6 semanas. Neurológicamente, mejoró de manera considerable. Por último, el cultivo de líquido cefalorraquídeo permitió aislar Histoplasma capsulatum. Se discuten las dificultades diagnósticas y el tratamiento de neurohistoplasmosis en pacientes inmunocompetentes, como también se intenta alertar acerca de la presencia de una cepa de Histoplasma capsulatum con afinidad por el sistema nervioso central.

Introduction Cryptococcosis is an opportunistic mycosis, especially in patients that are human immunodeficiency virus (HIV)-positive, and frequently involves the central nervous system. Methods We assessed the potential of ventriculoperitoneal shunting (VPS) in preventing mortality due to uncontrollable intracranial hypertension (ICH) in 15 patients with acquired immunodeficiency syndrome (AIDS)-related cryptococcal meningitis. Results After 2 weeks of antifungal therapy consisting of amphotericin B deoxycholate with or without fluconazole, patients with persistent ICH underwent VPS, despite having persistent Cryptococcus neoformans infection. In 12 patients, the uncontrollable ICH was resolved by VPS. Conclusions Patients with cryptococcal meningoencephalitis who have ICH must be considered for VPS even with positive cerebrospinal fluid cultures.

The frst case observed in Argentina of AIDS-related human penicillosis is herein presented. The patient was a six- teen year-old young man coming from a rural area of southern China. He was admitted at the F. J. Muñiz Hospital of Buenos Aires city with severe pneumonia and adult respiratory distress. Penicillium marneffei was isolated from bronchoalveolar lavage fuid and was microscopically observed in a skin cytodiagnosis. P. marneffei identifcation was confrmed by rRNA amplifcation and its phenotypic characteristics. The patient suffered an advanced HIV infection and also presented several AIDS-related diseases due to CMV, nosocomial bacterial infections and Pneumocystis jirovecii which led to a fatal outcome.

Se presenta el primer caso humano de peniciliosis por Penicillium marneffei observado en la República Argentina. El paciente era un joven de 16 años, HIV-positivo, procedente de un área rural del sur de China. El paciente fue internado en el Hospital "F. J. Muñiz" por padecer una neumonía grave con insufciencia respiratoria aguda. El agente causal fue aislado de un lavado broncoalveolar y se lo observó en un citodiagnóstico de piel. La identifcación de P. marneffei fue confrmada por las características fenotípicas del aislamiento y la amplifcación del ADNr. El enfermo padecía una infección muy avanzada por HIV que condujo a la aparición simultánea de infecciones por citomegalovirus, Pneumocystis jirovecii y procesos bacterianos nosocomiales. Este complejo cuadro derivó en una evolución fatal.

A histoplasmose disseminada é uma das doenças associadas à AIDS e relativamente comum, ocorrendo em quase 4% dos pacientes que vivem em áreas endêmicas e pode ser a primeira expressão clínica da infecção pelo HIV. Amplo espectro de lesões de pele associadas com a infecção pelo Histoplasma capsulatum têm sido descritas nos pacientes com AIDS, tais como máculas eritematosas, pápulas, nódulos e pústulas. Foram também relatadas lesões herpéticas, acneiformes, similares ao eritema multiforme, similares ao molusco contagioso, vasculíticas e esfoliativas. Em nosso conhecimento este é o primeiro caso de histoplamose disseminada em paciente com AIDS que se apresenta como erupção de aspecto rupióide.

Disseminated histoplasmosis is a relatively common AIDS-defining illness, occurring in almost 4% of patients living in endemic areas and it may be the first clinical expression of the HIV infection. A broad spectrum of clinical skin lesions associated with Histoplasma capsulatum infection have been described in AIDS patients, such as erythematous macules, papules, nodules, and pustules. Herpetic, acneiform, erythema multiforme-like, molluscum contagiosum-like, vasculitic, and exfoliative forms have also been reported. To our knowledge, this is the first case of disseminated histoplasmosis in an AIDS patient presented as a rupioid eruption.

Paracoccidioidomycosis is an endemic systemic disease in subtropical areas of Central and South America caused by a dimorphic fungus Paracoccidioides brasiliensis. Central nervous system involvement is a rare complication of the chronic disseminated disease that can affect the brain, cerebellum, brainstem and the spinal cord. The most frequent clinical form of neuroparacoccidiodomycosis is the cerebral abscess; with less frequency, the disease presents as a diffuse chronic meningoencephalitis. Here we present a patient with diagnosis of disseminated paracoccidioidomycosis and multiple cerebral lesions compatible with abscesses. Stereotactic biopsy followed by the microbiological and histopathological examination of the smears showed the characteristic yeast cells that confirmed the diagnosis of neuroparacoccidioidomycosis.

La paracoccidioidomicosis es una micosis sistémica, endémica de áreas tropicales y subtropicales de América Central y del Sur, causada por un hongo dimorfo denominado Paracoccidioides brasiliensis. El compromiso del sistema nervioso central es una rara complicación de la forma diseminada crónica de la enfermedad y puede comprometer el cerebro, el cerebelo, el tronco cerebral y la médula espinal. La forma clínica más común de la neuroparacoccidioidomicosis es el granuloma o absceso cerebral y, con menos frecuencia, la meningoencefalitis crónica. Se presenta un paciente con diagnóstico de paracoccidioidomicosis diseminada crónica con múltiples lesiones cerebrales compatibles con abscesos. La biopsia estereotáxica seguida del estudio histopatológico y microbiológico del material obtenido de las lesiones permitió observar las levaduras redondeadas con los brotes característicos de Paracoccidioides brasiliensis.

O abscesso do músculo psoas é uma infecção pouco comum que tem sido diagnosticada de maneira crescente nos últimos anos. Apresentamos um caso de paciente com infecção avançada pelo vírus da imunodeficiência humana (HIV) que desenvolveu uma infecção disseminada por Nocardia asteroides senso estrito tipo VI, com abscesso no psoas. Em nosso conhecimento, não foram relatados na literatura outros casos de abscesso do psoas por Nocardia, no contexto da infecção por HIV.

Psoas muscle abscess is an uncommon infection that have been diagnosed increasingly in the last years. We present a case of a patient with advanced human immunodeficiency virus infection who developed a disseminated infection due to Nocardia asteroides sensu stricto type VI with psoas abscess. To our knowledge no other cases of Nocardia psoas abscess in the setting of HIV infection have been reported in the literature.

Eumicetoma e cromoblastomicose são infecções fúngicas crônicas do tecido subcutâneo que evoluem com aspecto desfigurado, raramente involuindo espontaneamente. A maioria dos pacientes não apresenta melhora sustentada por longo tempo com os tratamentos disponíveis, sendo de grande importância as novas opções terapêuticas. A eficácia do posaconazol, um novo agente antifúngico de amplo espectro do grupo dos triazóis, foi estudada em 12 pacientes com eumicetoma ou cromoblastomicose refratária às terapêuticas antifúngicas disponíveis. Os pacientes receberam por no máximo 34 meses, doses divididas de 800 mg/dia de posaconazol. Resposta clínica parcial ou completa foi considerada como sucesso; doença estável ou falha terapêutica foi considerada como insucesso. Todos os 12 pacientes tinham infecções comprovadas ou prováveis, refratárias à terapêutica padrão preconizada. Sucesso clínico foi registrado em cinco de seis pacientes com eumicetoma e cinco de seis pacientes com cromoblastomicose. Em dois pacientes observou-se doença estável. Como parte do protocolo de extensão do tratamento, dois pacientes com eumicetoma que inicialmente tinham tido sucesso terapêutico e que após um intervalo maior de 10 meses apresentaram recidiva da micose, foram retratados com sucesso com posaconazol. Posaconazol foi bem tolerado durante o longo período de administração (até 1015 dias). A terapêutica com posaconazol foi seguida de sucesso na maioria dos pacientes com eumicetoma ou cromoblastomicose refratária à terapêutica padrão, sugerindo que tal droga possa ser uma importante opção no tratamento de tais doenças.

Eumycetoma and chromoblastomycosis are chronic, disfiguring fungal infections of the subcutaneous tissue that rarely resolve spontaneously. Most patients do not achieve sustained long-term benefits from available treatments; therefore, new therapeutic options are needed. We evaluated the efficacy of posaconazole, a new extended-spectrum triazole antifungal agent, in 12 patients with eumycetoma or chromoblastomycosis refractory to existing antifungal therapies. Posaconazole 800 mg/d was given in divided doses for a maximum of 34 months. Complete or partial clinical response was considered a success; stable disease or failure was considered a nonsuccess. All 12 patients had proven infections refractory to standard therapy. Clinical success was reported for five of six patients with eumycetoma and five of six patients with chromoblastomycosis. Two patients were reported to have stable disease. As part of a treatment-use extension protocol, two patients with eumycetoma who initially had successful outcome were successfully retreated with posaconazole after a treatment hiatus of > 10 months. Posaconazole was well tolerated during long-term administration (up to 1015 d). Posaconazole therapy resulted in successful outcome in most patients with eumycetoma or chromoblastomycosis refractory to standard therapies, suggesting that posaconazole may be an important treatment option for these diseases.

Paracoccidioidomycosis is one of the most frequent systemic and endemic mycoses of Latin America caused by a dimorphic fungus. In AIDS patients, paracoccidioidomycosis appears as a severe and disseminated disease with a wide spectrum of clinical findings. The CD4 counts are usually less than 200 cell/mu L. We present a case of disseminated paracoccidioidomycosis with peripleuritis and subcutaneous abscesses on the chest wall as initial manifestation of AIDS. In endemic countries, paracoccidioidomycosis should be included as an opportunistic infection in AIDS.

La paracoccidioidomicosis es una de las micosis sistémicas endémicas más frecuentes de Latinoamérica, causada por un hongo dimorfo. En los pacientes con SIDA se presenta como una enfermedad grave y diseminada, con un amplio espectro de manifestaciones clínicas. Los niveles de linfocitos T CD4 + son habitualmente < de 200 cél/myL. Presentamos un caso de paracoccidioidomicosis diseminada con peripleuritis y abscesos subcutáneos sobre la pared torácica como manifestación inicial del SIDA. En países endémicos, la paracoccidioidomicosis debe incluirse como una complicación oportunista de los pacientes con SIDA.

Histoplasmose disseminada aguda é uma entidade freqüente nos pacientes portadores do HIV. Na literatura internacional foram descritos trinta e cinco casos de endocardite causada por Histoplasma capsulatum, sendo todas as descrições correspondentes a histoplasmose disseminada subaguda. Este artigo relata o caso de um paciente HIV positivo com febre, dispnea, perda de peso, vômitos e poliadenopatias, no qual foi diagnosticado histoplasmose através de hemoculturas e isolamento do agente responsável das lesões cutâneas, e observadas vegetações na válvula aórtica durante uma ecocardiografia. O doente foi tratado com anfotericina B com boa evolução e as ecocardiografias posteriores não mostraram vegetações. Revisão da literautra sobre o tema foi realizada com ênfase especial quanto ao diagnóstico e tratamento dos casos anteriormente descritos.

Acute disseminated histoplasmosis is a frequent condition in HIV carriers. Thirty-five cases of endocarditis caused by Histoplasma capsulatum have been reported in international literature, and all these descriptions correspond to a context of subacute disseminated histoplasmosis. This paper presents the case of a HIV-positive patient with fever, dyspnea, weight loss, vomiting and polyadenopathies to whom histoplasmosis was diagnosed following blood-cultures and isolation of the agent responsible for cutaneous lesions, and in whom aortic-valve vegetations were found during an echocardiogram. The patient was treated with amphotericin B and had a good outcome; subsequent echocardiograms showed no vegetations. Literature on the subject is reviewed, with special emphasis on diagnosis and treatment of previously described cases.