Disseminated pulmonary histoplasmosis in immunocompetent patients: a common epidemiological exposure.

We describe the initial presentation, diagnostic work-up and treatment of three adult immunocompetent men who presented within a short time frame of each other to an academic medical centre with acute respiratory distress syndrome. Their presentation was found to be secondary to a large inoculum of histoplasmosis from remodelling a building with bat droppings infestation. We discuss the pathophysiology of histoplasmosis and highlight the importance of exposure history in patients with acute respiratory failure and why patients with the occupational risk of exposure to fungal inoculum should wear protective respirator gear.

Paracoccidioides spp. and Histoplasma capsulatum: Current and New Perspectives for Diagnosis and Treatment.

The thermally-dimorphic systemic fungal group includes several important human pathogens: Blastomyces dermatitides, Coccidioides immitis and C. posadasii, Histoplasma capsulatum, Paracoccidioides brasiliensis, P. lutzii, and Talaromyces (Penicillium) marneffei. They usually are geographically restricted and have natural habitats in soil or in plants, and when fungal propagules invade mammalian host by inhalation, they initiate an inflammatory reaction that can result in self-resolution of the infection or cause an acute or chronic disease. In the setting of the AIDS pandemic and the developments in modern medicine, such as immunosuppressive therapy in cancer surgery patients and in transplantation and autoimmune diseases, the incidence of endemic mycoses has progressively increased. Another important factor of the increased incidence of systemic mycoses in certain regions is the progressive devastation of tropical and subtropical forests. In this review, we focus on two of the most important systemic mycoses: paracoccidioidomycosis and histoplasmosis, and their major characteristics in epidemiology, clinical aspects and laboratorial diagnosis.

Histoplasmosis in HIV-positive patients in Ceará, Brazil: clinical-laboratory aspects and in vitro antifungal susceptibility of Histoplasma capsulatum isolates.

This study contains a descriptive analysis of histoplasmosis in AIDS patients between 2006 and 2010 in the state of Ceará, Brazil. Additionally, the in vitro susceptibility of Histoplasma capsulatum isolates obtained during this period was assessed. We report 208 cases of patients with histoplasmosis and AIDS, describing the epidemiological, clinical, laboratory and therapeutic aspects. The in vitro antifungal susceptibility test was carried out by the microdilution method, according to Clinical and Laboratory Standards Institute, with H. capsulatum in the filamentous and yeast phases, against the antifungals amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin. In 38.9% of the cases, histoplasmosis was the first indicator of AIDS and in 85.8% of the patients the CD4 cell count was lower than 100 cells/mm(3). The lactate dehydrogenase levels were high in all the patients evaluated, with impairment of hepatic and renal function and evolution to death in 42.3% of the cases. The in vitro susceptibility profile demonstrated there was no antifungal resistance among the isolates evaluated. There was a significant increase in the number of histoplasmosis cases in HIV-positive patients during the period surveyed in the state of Ceará, northeastern Brazil, but no antifungal resistance among the recovered isolates of H. capsulatum.

An unusual cutaneous tumor: African histoplasmosis following mudbaths: case report and review.

African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is endemic in Africa. The disease usually involves the skin, subcutaneous tissue, and bones. A case of African histoplasmosis presenting as a cutaneous tumor and non-healing wound in a 66-year-old immunocompetent male residing in Africa, the first ever reported following mudbaths and acupuncture, is hereby reported. Diagnosis was confirmed by means of polymerase chain reaction performed on tissue material. The patient was started on long-term itraconazole therapy and he responded well. African histoplasmosis should be included in the differential diagnosis of non-healing wounds or tumor-like lesions, especially in the context of mudbaths in an endemic area.

Validation and clinical application of a molecular method for identification of Histoplasma capsulatum in human specimens in Colombia, South America.

The conventional means of diagnosis of histoplasmosis presents difficulties because of the delay to the time that the diagnosis is made, indicating the need for the implementation of molecular assays. We evaluated 146 clinical samples from 135 patients suspected of having histoplasmosis using a previously reported nested PCR assay for the Histoplasma capsulatum-specific 100-kDa protein (the Hc100 PCR). In order to determine the specificity of this molecular test, we also used samples from healthy individuals (n = 20), patients suspected of having respiratory disease with negative fungal cultures (n = 29), and patients with other proven infections (n = 60). Additionally, a sizable collection of DNA from cultures of H. capsulatum and other medically relevant pathogens was studied. A panfungal PCR assay that amplified the internal transcribed spacer 2 region was also used to identify all fungal DNAs. All PCR-amplified products were sequenced. Of the 146 clinical samples, 67 (45.9%) were positive by culture and PCR, while 9 samples negative by culture were positive by PCR. All the sequences corresponding to the 76 amplified products presented > or =98% identity with H. capsulatum. The Hc100 PCR exhibited a sensitivity of 100% and specificities of 92.4% and 95.2% when the results were compared to those for the negative controls and samples from other proven clinical entities, respectively; the positive predictive value was 83% and the negative predictive value was 100%; the positive and negative likelihood rates were 25 and 0, respectively. These results suggest that the Hc100 nested PCR assay for the detection of H. capsulatum DNA is a useful test in areas where mycosis caused by this organism is endemic.

Unusual manifestation of histoplasmosis in connective tissue diseases.

This report describes the coexistence of three patients with rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis) and infections because of Histoplasma capsulatum. Connective tissue diseases and histoplasmosis share several clinical findings. Therefore, histoplasmosis could be misdiagnosed as connective tissue disease or a flare of these diseases. Such cases highlight the importance of awareness of histoplasmosis in immunocompromised patients, particularly in those originating from endemic areas.

Manifestaciones orales de patologías tropicales / Oral manifestations of tropical diseases

El presente trabajo expone las características clínias e histopatológicas de las pricnipales patologías tropicales (micóticas, parasitarias y virales) que presentan manifestaciones bucales, poniendo énfasis en la paracoccidioidomicosis, histoplasmosis, critpcocosis, dengue, leishmaniasis e infección micótica (AU)

Hypothesis on the mechanism of resistance to fluconazole in Histoplasma capsulatum.

An AIDS patient with disseminated histoplasmosis who improved during treatment with fluconazole but remained fungemic and subsequently relapsed is described. Isolates obtained from blood during therapy showed a progressive increase in fluconazole MIC from 0.625 to 20 micrograms/ml. The pretreatment, or parent, isolate and the posttreatment, or relapse, isolate demonstrated identical genetic patterns by PCR fingerprinting with three different primers. Fluconazole was less potent inhibitor of the growth of the relapse isolate than of the pretreatment isolate (50% inhibitory concentration [IC50] = 11.7 microM), while itraconazole was more potent (relapse isolate IC50 = 0.0011 microM versus pretreatment isolate IC50 = 0.0064 microM). Neither the increased sensitivity to itraconazole nor the decreased activity of fluconazole on the growth of the relapse isolate results from changes in the intracellular content of these agents. To reach 50% inhibition of ergosterol synthesis in both the parent and relapse isolates, about 2 nM itraconazole was needed; with fluconazole, 50% inhibition was achieved at 20.9 microM and 55.5 microM, respectively. Resistance to fluconazole may develop during treatment and results from decreased sensitivity of ergosterol synthesis.

[Histoplasmosis: clinical, biological, and therapeutic aspects in ten cases (author's transl)]. / Dix cas d'histoplasmose: aspects cliniques, biologiques et thérapeutiques.

The authors present 10 cases of histoplasmosis, 3 due to H. capsulatum, and 7 to H. duboisii. The presenting signs were stomatological or laryngeal with H. capsulatum, and ganglionic, cutaneous, or skeletal with H. duboisii. Diagnosis was confirmed by the discovery of histoplasms in the lesions: 7 times the examination of a needle biopsy sample was positive; in 8 cases out of 10, culture on Sabouraud's medium was positive; in 3 cases out of 4 the inoculated hamster showed the presence of a histoplasmosis. Histological examination of lesions biopsies demonstrated histoplasms in the 9 cases studied. The intradermal reaction to histogical examination of lesion biopsies demonstrated histoplasms in the 9 cases studied. The intradermal reaction to histoplasmin, positive in only 1 out of 7 cases, and serological tests which showed precipitating antibodies in only 4 cases out of 10, are of very little diagnostic value. All patients were treated with amphotericin B, sometimes associated with clotrimazole (3 cases), miconazole (1 case), and rifampicin (2 cases). Two relapses occurred, one, after too soon an interruption of treatment relapsed two months later, and the other followed 18 months after a total dose of 4,200 mg of amphotericin. Surgical treatment of active subcutaneous ganglionic and bony foci may be necessary, and was employed in three cases, with a favourable result in a case of severe disseminated histoplasmosis.