American Tegumentary Leishmaniasis: case series describing an enigmatic and neglected disease / Leishmaniasis americana tegumentaria: series de casos describiendo una enigmática y olvidada enfermedad

Abstract American Tegumentary Leishmaniasis (ATL) is an infectious disease affecting the skin and mucous membranes. ATL is caused by parasites of the Leishmania genus with around one million cases are reported each year worldwide. This paper describes three rare cases of tegumentary leishmaniasis treated at a tropical disease research center.

Resumen La Leishmaniasis Tegumentaria Americana es una enfermedad infecciosa que afecta la piel y las mucosas. La ATL es causada por parásitos del género Leishmania y cada año se reportan alrededor de un millón de casos en todo el mundo. Este artículo describe tres casos raros de leishmaniasis tegumentaria tratados en un centro de investigación de enfermedades tropicales.

Pulmonary Histoplasmosis.

Histoplasmosis is one of the most frequent causes of fungal respiratory infection in endemic regions, has a broad spectrum of clinical manifestations and can present in several forms. The extent of disease is determined by the number of conidia inhaled, the immune response of the host and the integrity of the respiratory tract. From an initial and most benign form, acute pulmonary histoplasmosis (an influenza-like illness that is typically asymptomatic or mild in persons without prior immune compromise), histoplasmosis can become a lifethreatening progressive disseminated infection (PDH) that affects mainly immunocompromised patients, with high morbidity and mortality. Chronic pulmonary histoplasmosis is an uncommon manifestation of Histoplasma infection, with features similar to pulmonary tuberculosis, and if it remains undiagnosed or untreated it also can cause significant morbidity. Some rare but serious complications may also occur that are produced by an excessive immune response, such as mediastinal fibrosis, histoplasmoma and broncholithiasis. Histoplasmosis is highly endemic in regions of North, Central and South America as well as being reported in parts of Asia and Africa. The risk of histoplasmosis is greatest in patients with HIV infection, especially those with CD4+ counts of <200 cells/µL. We review clinical manifestations, radiological findings and treatment options according to the clinical form (induction therapy and maintenance therapy), as well as different diagnosis tools and new laboratory tests that have been recently developed and validated and are becoming widely available. These should have an impact in reducing time for diagnosis and starting therapy and in reducing morbidity and mortality, especially in patients with HIV infection, where histoplasmosis is currently estimated to be responsible for 5-15% of AIDS-related deaths.

Response to therapy in patients with cryptococcosis and AIDS: association with in vitro susceptibility to fluconazole / Respuesta al tratamiento en pacientes con criptococosis y sida: relación con la sensibilidad in vitro al fluconazol

Background. The implications of the Cryptococcus neoformans resistance to fluconazole on patient therapy have not been fully elucidated due to the discordant results found in published studies. Aims. To establish the influence of C. neoformans resistance to fluconazole in the therapy of individuals with cryptococcosis and AIDS. Methods. This study retrospectively compared the clinical course of patients with cryptococcosis according to the level of fluconazole resistance of their C. neoformans isolates. Results. This study included 71 episodes of cryptococcosis, defined as those isolates of C. neoformans obtained from patients with mycosis, of which 36 isolates were sensitive to fluconazole, 20 susceptible dose-dependent (SDD), and 15 were resistant. There were 5 treatment failures in the consolidation phase; two occurred in patients who had a susceptible strain, 2 in patients who had SDD strains, and one in a patient who had a resistant strain. During the maintenance treatment, relapses occurred in 4 of 33 patients (12%), seen during the follow-up period, none of which occurred in the group with resistant isolates. There were no significant differences in survival time free of treatment failure (p = 0.65) or survival time free of failure or relapse (p = 0.38). These results were not affected when tested in a Cox model that included age, CD4T lymphocyte counts, and use of antiretroviral therapy. Conclusions. In HIV patients with cryptococcosis, the resistance of C. neoformans appeared not to increase the risk of failure or relapse during treatment (AU)

Antecedentes. Las implicaciones de la resistencia de Cryptococcus neoformans al fluconazol en el tratamiento de pacientes infectados con esta levadura no han sido completamente definidas debido a hallazgos discordantes obtenidos previamente. Objetivos. Dilucidar la influencia de la resistencia de C. neoformans al fluconazol en el tratamiento de los pacientes con criptococosis y sida. Métodos. En este estudio se compara retrospectivamente la evolución clínica de los pacientes con criptococosis según el grado de resistencia al fluconazol de los aislamientos de C. neoformans obtenidos de ellos. Resultados. Se incluyeron 71 episodios de criptococosis definidos por el aislamiento de C. neoformans de pacientes con la micosis, que se distribuyeron de la siguiente manera: 36 aislamientos fueron sensibles, 20 sensibles dosis-dependiente y 15 resistentes. En la fase de consolidación, cinco fallos en el proceso de tratamiento tuvieron lugar: dos en pacientes con aislamientos sensibles, dos en pacientes con aislamientos dosis-dependiente y uno en un paciente con un aislamiento resistente. Durante la fase de mantenimiento se presentaron 4 recurrencias en los 33 pacientes que tuvieron seguimiento (12%), ninguna de las cuales ocurrió en el grupo con aislamientos resistentes. No se encontraron diferencias estadísticamente significativas en el tiempo de supervivencia de los casos sin fallo terapéutico (p = 0.65) o en el tiempo de supervivencia de los casos sin fallo terapéutico o recaída (p = 0.38). Estos resultados no se modificaron cuando fueron evaluados en un modelo de regresión de Cox en el que se incluyeron la edad, el conteo de linfocitos T CD4 y el uso de terapia antirretroviral. Conclusiones. En pacientes con VIH y criptococosis la resistencia de C. neoformans a fluconazol parece no incrementar el riesgo de fallo terapéutico o recaída (AU)

Implementation of a Training Course Increased the Diagnosis of Histoplasmosis in Colombia.

Histoplasmosis causes a significant mortality, especially persons living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) from developing countries where access to both appropriate diagnostic methods and antiretroviral therapy are limited. A total of 81 physicians assigned to 17 Colombian departments (states) received training in the clinical, epidemiological, and diagnostic aspects of histoplasmosis. Once this training was received and during the period of October 2009-November 2012, these physicians sent biological samples for immunodiagnostic, mycological, and molecular tests from their patients with suspicion of histoplasmosis. A total of 1,536 samples from 768 patients were evaluated. Of the 768 patients studied, 463 (60%) were HIV positive, 214 (28%) HIV negative, and in 91 (12%) this diagnosis was unknown, and 538 (70%) were males. The 1,536 specimens studied comprised 722 sera, 439 blood samples, and 241 urines, which were tested by immunodiffusion (ID), culture, and antigenuria, respectively; in addition, 134 specimens were tested by performing a molecular assay. Histoplasmosis was diagnosed in 133 patients (17%). After the training, we observed more diagnoses from 27 to 44 cases per year. In this study, a significantly increased number of histoplasmosis cases reported by year were observed after implementing an educational training program.

Response to therapy in patients with cryptococcosis and AIDS: Association with in vitro susceptibility to fluconazole.

BACKGROUND: The implications of the Cryptococcus neoformans resistance to fluconazole on patient therapy have not been fully elucidated due to the discordant results found in published studies. AIMS: To establish the influence of C. neoformans resistance to fluconazole in the therapy of individuals with cryptococcosis and AIDS. METHODS: This study retrospectively compared the clinical course of patients with cryptococcosis according to the level of fluconazole resistance of their C. neoformans isolates. RESULTS: This study included 71 episodes of cryptococcosis, defined as those isolates of C. neoformans obtained from patients with mycosis, of which 36 isolates were sensitive to fluconazole, 20 susceptible dose-dependent (SDD), and 15 were resistant. There were 5 treatment failures in the consolidation phase; two occurred in patients who had a susceptible strain, 2 in patients who had SDD strains, and one in a patient who had a resistant strain. During the maintenance treatment, relapses occurred in 4 of 33 patients (12%), seen during the follow-up period, none of which occurred in the group with resistant isolates. There were no significant differences in survival time free of treatment failure (p=0.65) or survival time free of failure or relapse (p=0.38). These results were not affected when tested in a Cox model that included age, CD4T lymphocyte counts, and use of antiretroviral therapy. CONCLUSIONS: In HIV patients with cryptococcosis, the resistance of C. neoformans appeared not to increase the risk of failure or relapse during treatment.

Diagnostic value of culture and serological tests in the diagnosis of histoplasmosis in HIV and non-HIV Colombian patients.

We determined the value of culture and serological tests used to diagnose histoplasmosis. The medical records of 391 histoplasmosis patients were analyzed. Diagnosis of the mycosis was assessed by culture, complement fixation, and immunodiffusion tests; 310 patients (79.5%) were male, and 184 patients (47.1%) were infected with human immunodeficiency virus (HIV). Positivity value for cultures was 35.7% (74/207), reactivity of serological tests was 95.2% (160/168), and a combination of both methodologies was 16.9% (35/207) for non-HIV patients. Positivity value for cultures was 75.0% (138/184), reactivity of serological tests was 92.4% (85/92), and a combination of both methodologies was 26.0% (48/184) for HIV/acquired immunodeficiency syndrome (AIDS) patients; 48.1% (102/212) of extrapulmonary samples from HIV/AIDS patients yielded positive cultures compared with 23.1% (49/212) in non-HIV patients. Lymphocyte counts made for 33.1% (61/184) of HIV/AIDS patients showed a trend to low CD4+ numbers and higher proportion of positive cultures. These results indicate that culture is the most reliable fungal diagnostic method for HIV/AIDS patients, and contrary to what is generally believed, serological assays are useful for diagnosing histoplasmosis in these patients.

Identification of Paracoccidioides brasiliensis in adrenal glands biopsies of two patients with paracoccidioidomycosis and adrenal insufficiency.

The authors report two cases of adrenal insufficiency secondary to infiltration of the adrenal glands by Paracoccidioides brasiliensis. The first patient had been treated for a chronic multifocal form of paracoccidiodomycosis 11 years ago. The diagnosis of the mycosis was done simultaneous with that of the adrenal insufficiency in the second patient. In both patients the diagnosis was done by direct visualization of fungus in adrenal biopsies. They were treated with hormonal supplements and itraconazol by 12 and six months, without relapses during the follow-up period.

Identification of Paracoccidioides brasiliensis in adrenal glands biopsies of two patients with paracoccidioidomycosis and adrenal insufficiency / Identificação do Paracoccidioides brasiliensis nas amostras de glândulas adrenais de dois doentes com paracoccidioidomicose e insuficiência adrenal

The authors report two cases of adrenal insufficiency secondary to infiltration of the adrenal glands by Paracoccidioides brasiliensis. The first patient had been treated for a chronic multifocal form of paracoccidiodomycosis 11 years ago. The diagnosis of the mycosis was done simultaneous with that of the adrenal insufficiency in the second patient. In both patients the diagnosis was done by direct visualization of fungus in adrenal biopsies. They were treated with hormonal supplements and itraconazol by 12 and six months, without relapses during the follow-up period.

Os autores apresentam dois casos de insuficiência supra-renal secundária à infiltração das adrenais pelo Paracoccidioides brasiliensis. O primeiro paciente tinha sido tratado de paracoccidioidomicose crônica multifocal 11 anos atrás. No segundo paciente, o diagnóstico da micose foi feito de forma simultânea com o da insuficiência adrenal. Em ambos os pacientes, o diagnóstico foi feito pela visualização direta do fungo nas biopsias adrenais. Eles foram tratados com suplementos hormonais com itraconazol por seis a 12 meses, sem recaídas durante o período de acompanhamento.

Sensibilidad a fluconazol y voriconazol de aislamientos de Candida spp., obtenidos de mucosa oral de pacientes con sida / Sensitivity to Fluconazol and Voriconazol in Candida spp. isolates from the oral mucosa of HIV positive patients

Se determinó la sensibilidad al fluconazol y al voriconazol de aislamientos de Candida spp. obtenidosde la mucosa oral de 54 pacientes con sida hospitalizadosen la ESE Hospital La María (Medellín, Colombia). además, se comprobó la especie de tales aislamientos.Los pacientes eran todos adultos (promedio de 40,5 años, rango de 23 a 56) y la mayoría (77,8 por ciento) hombres. En 40 (71,1 por ciento) de ellos se obtuvo crecimiento de Candida spp. y en 6 (11,1por ciento) se aisló más de una especie de Candida. La clasificación a especie reveló C. albicans, C. krusei, C. tropicalis, C.parapsilosis y C. glabrata. La determinación de lasensibilidad in vitro se hizo por difusión en agar con las especificaciones del CLSI de Estados Unidos (M44P). El 72,9 por ciento de los aislamientos de Candida spp. fueron sensibles al fluconazol; 6,3 por ciento, sensibles dependientes de la dosis, y 20,8 por ciento, resistentes. Para el voriconazol, 89,6 por ciento fueron sensibles; 8,3 por ciento, sensibles dependientes de la dosis y 2,1 por ciento, resistentes. La resistencia se observó en C. albicans y C. krusei. Estos resultados demuestran la efectividad de ambos antimicóticos y fue mayor la correspondiente al voriconazol. Igualmente se señala la importancia de las pruebas in vitro puesto que en pacientes con VIH/sida pueden encontrarse especies resistentes. Se ratifica la importancia de la clasificación por especiede las levaduras del género Candida.

Tuberculosis pulmonar y diabetes mellitus: presentacion de un caco clinico / Pulmonary tuberculosis and diabetes mellitus: presentation of a clinical case

Los pacientes diabeticos son mas propensos a las infecciones bacterianas, entre ellas la tuberculosis. Se ha informado que esta entidad es 3-4 veses mas frecuente en pacientes diabeticos que en los que no lo son. En estos pacientes la tuberculosis presenta uncompromiso pulmonar atipico en comparacion con los pacientes no diabeticos. existe, ademas, una pobre respuesta al tratamiento antituberculoso, por lo que se recomienda prolongarlo hasta completar los 9 meses. se presenta el caso de un hombre de 59 años, conun cuadro de 3 semanas de evolucion consistente en perdida de peso, astenia, adinamia y tos seca. El paciente ha sido diabetico por 4 años. Los Rx y la broncoscopia mostraron compromiso del campo pulmonar izquierdo. El cultivo del sepillado bronquial para M. tuberculosis fue positivo a las 5 semanas. El paciente fue tratado con medicamentos antituberculosos convencionales, pero la segunda fase del tratamiento fue prolongada hasta completar 9 meses. Egreso del programa por curacion.

[Adrenal gland insufficiency secondary to paracoccidioidomycosis]. / Insuficiencia suprarrenal secundaria a paracoccidioidomicosis.

Paracoccidioidomycosis is regularly associated with adrenal insufficiency in 10-15% of symptomatic cases, and in some instances, diagnosis of the mycosis precedes the adrenal manifestation. To establish the frequency of this association, records were reviewed of 207 cases diagnosed with mycosis at the Mycology Service of the Corporación para Investigaciones Biológicas. Six cases (2.9%) were found to have adrenal insufficiency. Patients were all males with a mean age of 67.2 years (range 48-75) and most worked in agriculture. The duration of the symptoms of adrenal damage was 4.1 months (range 2-6). All patients experienced weight loss and malaise; all had abnormal lung X-rays. Major clinical improvement was recorded after initiation of the specific treatments consisting of itraconazole, prednisolone and fluorcortisone. Diminished antibody titers against Paracoccidioides brasiliensis were also recorded after treatment. Prompt treatment re-established adrenal function and effected recovery of normal gland morphology. Consequently, early detection of hypoadrenalism in patients living in the endemic areas is necessary to avoid further adrenal damage and permits a shorter hormonal treatment period in patients afflicted by the mycosis.

Insuficiencia suprarrenal secundaria a paracoccidioidomicosis / Adrenal gland insufficiency secondary to paracoccidioidomycosis

Paracoccidioidomycosis is regularly associated with adrenal insufficiency in 10-15 of symptomatic cases, and in some instances, diagnosis of the mycosis precedes the adrenal manifestation. To establish the frequency of this association, records were reviewed of 207 cases diagnosed with mycosis at the Mycology Service of the Corporación para Investigaciones Biológicas. Six cases (2.9) were found to have adrenal insufficiency. Patients were all males with a mean age of 67.2 years (range 48-75) and most worked in agriculture. The duration of the symptoms of adrenal damage was 4.1 months (range 2-6). All patients experienced weight loss and malaise; all had abnormal lung X-rays. Major clinical improvement was recorded after initiation of the specific treatments consisting of itraconazole, prednisolone and fluorcortisone. Diminished antibody titers against Paracoccidioides brasiliensis were also recorded after treatment. Prompt treatment re-established adrenal function and effected recovery of normal gland morphology. Consequently, early detection of hypoadrenalism in patients living in the endemic areas is necessary to avoid further adrenal damage and permits a shorter hormonal treatment period in patients afflicted by the mycosis.

[Outbreak of acute histoplasmosis in a family group: identification of the infection source]. / Brote de histoplasmosis aguda en un grupo familiar: identificación de la fuente de infección.

An outbreak of acute histoplasmosis occurring in 4 members of the same family, two women, a girl and a male, is reported. The index case presented acute respiratory symptoms, severe enough to require hospitalization. In the remaining persons, the infection was asymptomatic but was evidenced by reactive histoplasmin serologic tests. Search for the common source of infection led to an enriched soil obtained in a local nursery for growing in-door plants. BALB/c mice were inoculated with suspensions of soils from the potted plants. Histoplasma capsulatum var. capsulatum was isolated from various internal organs of the mice. Although histoplasmosis is observed more frequently in persons with occupations implying risk of exposure and is connected to rural areas, outbreaks and intra-family cases are now common in urban areas. This is due to massive urbanization, deforestation, demolitions and the use of soils enriched with organic compounds, mainly bird/bat excrements. This report calls the attention on the danger involved in using such enriched soils for plant nutrition.

Brote de histoplasmosis aguda en un grupo familiar: identificación de la fuente de infección / Acute histoplasmosis outbreack in a family group: identification of infection source

Se informa un brote de histoplasmosis ocurrido en los integrantes de una familia y que comprometió a cuatro personas, dos mujeres, una niña y un hombre. El caso índice consultó por sintomatología respiratorio grave, de comienzo súbito, que requirió hospitalización. En los otros casos, la infección curso de manera asintomática pero se puso en evidencia por la reactividad en las pruebas serológicas con histoplasmina. La búsqueda de una fuente común de contagio llevó a sospechar que era la tierra de un vivero que se había utilizado como fertilizante de las plantas caseras. Las supensiones de las tierras de las mecetas sirvieron para inocular ratones BALB/c, de cuyos órganos fue posible aislar el agente etiológico, Histoplasma capsulatum var. capsulatum. Si bien la histoplasmosis es más frecuente en ciertas ocupaciones y es propia de áreas rurales, las epidemias y los brotes son ahora comunes en áreas urbanas debido a actividades como la urbanización masiva, la tala de árboles, las demoliciones y el uso de tierras enriquecidas con abonos orgánicos (gallinaza, guano). Se llama la atención sobre el peligro que representa esta última actividad

Tratamiento de la tuberculosis multirresistente / The treatment of multidrug-resistant tuberculosis

La magnitud y el impacto futuros del actual problema de la resistencia de las micobacterias a los medicamentos antituberculosos es aun desconocido. La OMS estima que, al presente, existen 50 millones de personas infectadas con bacilos multirresistentes. Su programa de vigilancia en tuberculosis informó en l994, la existencia de este fenómeno en todo el mundo, con prevalencias de multirresistencia primaria de 1,4 por ciento (rango 0-14,4) y secundaria de 13 por ciento (rango 0-54), observándose los más altos niveles en Rusia, Corea del Sur y Argentina. Las técnicas de biología molecular han permitido demostrar las alteraciones genéticas que ocurren para la expresión clínica de este fenómeno, siendo el principal mecanismo de presión los tratamientos inadecuados ya que ellos seleccionan las cepas multirresistentes de Mycobacterium tuberculosis. El tratamiento de un paciente infectado por micobacterias multirresistentes debe ser prolongado y conducido con fármacos de segunda línea, los cuales son no sólo difíciles de conseguir y muestran ser menos efectivos sino que, además, son mucho más costosos que aquellos de primera línea. Se estima que el tratamiento con los medicamentos de reserva, tiene un costo de US $ 5.000 – 7.000. Por consiguiente, todos los esfuerzos deben ser dirigidos hacia la prevención de este fenómeno a través de tratamientos controlados ya que los países en desarrollo no están en capacidad de proveer el tratamiento alterno

El caso de infecciosas: paracoccidioidomicosis: presentacion inusal en un paciente joven / The case of infectious diseases: paracoccidioidomycosis: inusal presentation in a young patient

Se presenta el caso de un hombre de 24 años, agricultor, quien consultó al Hospital Marco Fidel Suárez de Bello por un cuadro de año y medio de evolución, consistente en la presencia de una masa en el testículo derecho y dos meses de pérdida de peso e ictericia. La ecografía y la TAC de abdomen mostraron obstrucción del árbol biliar distal, nódulos retroperitoneales e inguinales, hepatoesplenomegalia, aumento del páncreas e hidrocele bilateral. Se realizó laparotomía exploradora y se tomaron biopsias mesentéricas, que revelaron abundantes levaduras con gemación múltiple, compatible con Paracoccidioides brasiliensis. Las pruebas serológicas reforzaron este diagnóstico. Se comenzó tratamiento con itraconazol, 200 mg al día. Después de 2 meses de tratamiento, la respuesta ha sido satisfactoria. Este caso ilustra el polimorfismo de la paracoccidioidomicosis y la necesidad de considerarla en el diagnóstico diferencial de otras patologías del sistema retículo endotelial.

El caso de infecciosas. Coccidioidomicosis pulmonar: informe de un caso autóctono / The case of infectious pulmonary coccidioidomycosis of an indigenous: case report

Se presenta el caso de un hombre de 52 años, tractorista, proveniente de Pinto, Magdalena, quien consultó al Hospital Universitario San Vicente de Paúl, por un cuadro de un mes y medio de evolución de fiebre alta, escalofríos, sudoración nocturna, astenia, adinamia, anorexia y pérdida de peso. El diagnóstico de coccidioidomicosis fue realizado por biopsia y confirmado por directo, cultivo, pruebas de fijación de complemento e intradermorreacción. Se realizó tratamiento con itraconazol a dosis de 200 mg. /día por un año, con desaparición de su sintomatología. Dos años después del diagnóstico y un año post-terapia, el paciente se encuentra en excelentes condiciones.