Feo-hifomicose subcutânea por Exophiala jeanselmei: registro de três casos em transplantados renais

São registrados três casos de feo-hifornicose subcutânea em transplantados renais provocados pela Exophiala jeanselmei (Langeron) McGinnis et Padhye 1977, fungo demácio capaz, também, de produzir raramente eumicetoma de grãos pretos. Este fungo, segundo KWON-CHUNG & BENNETT, 1992(27) é antigenicamente muito heterogêneo, sendo identificados até o presente momento três sorotipos com subgrupos dentro de cada um deles. A feo-hifomicose subcutânea vem se tornando cada vez mais freqüente em transplantados renais, submetidos a terapêutica imunodepressora. Como a Exophiala jeanselmei já foi isolada do meio ambiente, torna-se dificil explicar a patogenia desses casos por um despertar ou reativação de processos quiescentes. Os Autores fizeram ampla revisão da literatura, registrando principalmente os casos de feo-hifomicose publicados no Brasil. Sugerem também, eventual ação fungistática da ciclosporina A sobre a Exophiala jeanselmei.

Molecular details of INH-C-10 binding to wt KatG and Its S315T mutant

Isoniazid (INH) is still one of the two most effective antitubercular drugs and is included in all recommended multitherapeutic regimens. Because of the increasing resistance of Mycobacterium tuberculosis to INH, mainly associated with mutations in the katG gene, new INH-based compounds have been proposed to circumvent this problem. In this work, we present a detailed comparative study of the molecular determinants of the interactions between wt KatG or its S315T mutant form and either INH or INH-C10, a new acylated INH derivative. MD simulations were used to explore the conformational space of both proteins, and results indicate that the S315T mutation did not have a significant impact on the average size of the access tunnel in the vicinity of these residues. Our simulations also indicate that the steric hindrance role assigned to Asp137 is transient and that electrostatic changes can be important in understanding the enzyme activity data of mutations in KatG. Additionally, molecular docking studies were used to determine the preferred modes of binding of the two substrates. Upon mutation, the apparently less favored docking solution for reaction became the most abundant, suggesting that S315T mutation favors less optimal binding modes. Moreover, the aliphatic tail in INH-C10 seems to bring the hydrazine group closer to the heme, thus favoring the apparent most reactive binding mode, regardless of the enzyme form. The ITC data is in agreement with our interpretation of the C10 alkyl chain role and helped to rationalize the significantly lower experimental MIC value observed for INH-C10. This compound seems to be able to counterbalance most of the conformational restrictions introduced by the mutation, which are thought to be responsible for the decrease in INH activity in the mutated strain. Therefore, INH-C10 appears to be a very promising lead compound for drug development.

Aspergillosis in immunocompromised children acute myeloid leukemia and bone marrow aplasia.: Report of two cases

Two cases of Aspergillosis in immunocompromised children are reported. Both were caused by Aspergillns flavus. Early diagnosis and treatment led to the remission of the process. One patient had acute myeloid leukemia; the fungus was isolated from the blood. The other patient with bone marrow aplasia, presented an invasive aspergillosis of the paranasal sinuses with dissemination of fungal infection; the diagnosis was obtained by histology and culture of biopsied tissue from a palatal ulceration.

Subcutaneous hyalohyphomycosis caused by Acremonium recifei: case report

We present a case of subcutaneous hyalohyphomycosis due to Acremonium recifei, a species whose habitat is probably the soil, first identified in 1934 by Arêa Leão and Lobo in a case of podal eumycetoma with white-yellowish grains and initially named Cephalosporium recifei. A white immunocompetent female patient from the state of Bahia, Brazil, with a history of traumatic injury to the right hand is reported. The lesion was painless, with edema, inflammation and the presence of fistulae. Seropurulent secretion with the absence of grains was present. Histopathological examination of material stained with hematoxylin-eosin showed hyaline septate hyphae. A culture was positive for Acremonium recifei. Treatment with itraconazole, 200 mg/day, for two months led to a favorable course and cure of the process. We report for the first time in the literature a case of subcutaneous hyalohyphomycosis due to Acremonium recifei in a immunocompetent woman. Treatment with itraconazole 200 mg/day, for two months, resulted in cure.

Immunological status of ENL (Erythema Nodosum Leprosum) patients: its relationship to bacterial load and levels of circulanting IL-2R

Recent data suggest that the clinical course of reactional states in leprosy is closely related to the cytokine profile released locally or systemically by the patients. In the present study, patients with erythema nodosum leprosum (ENL) were grouped according to the intensity of their clinical symptoms. Clinical and immunological aspects of ENL and the impact of these parameters on bacterial load were assessed in conjunction with patients' in vitro immune response to mycobacterial antigens. In 10 out of the 17 patients tested, BI (bacterial index) was reduced by at least 1 log from leprosy diagnosis to the onset of their first reactional episode (ENL), as compared to an expected 0.3 log reduction in the unreactional group for the same MDT (multidrug therapy) period. However, no difference in the rate of BI reduction was noted at the end of MDT among ENL and unreactional lepromatous patients. Accordingly, although TNF-alpha (tumor necrosis factor) levels were enhanced in the sera of 70.6% of the ENL patients tested, no relationship was noted between circulating TNF-alpha levels and the decrease in BI detected at the onset of the reactional episode. Evaluation of bacterial viability of M. leprae isolated from the reactional lesions showed no growth in the mouse footpads. Only 20% of the patients demonstrated specific immune response to M. leprae during ENL. Moreover, high levels of soluble IL-2R (interleukin-2 receptor) were present in 78% of the patients. Circulating anti-neural (anti-ceramide and anti-galactocerebroside antibodies) and anti-mycobacterial antibodies were detected in ENL patients' sera as well, which were not related to the clinical course of disease. Our data suggest that bacterial killing is enhanced during reactions. Emergence of specific immune response to M. leprae and the effective role of TNF-alpha in mediating fragmentation of bacteria still need to be clarified.

Basidiomycosis: a review of the literature

The basidiomycosis, fungal infections provoked by basidiomycetes or agaric fungi have been recorded at growing frequencies in the medical literature, especially after the advent of AIDS in 1991. The basidiospores of these fungi, scattered in the atmosphere and transported by winds or air currents, reach the maxillary sinuses through the nasal route, most of the times causing signs and symptoms of chronic sinusitis. Basidiomycetes have also been isolated from sputum, especially Schizophyllum commune. Lesions of the buccal mucosa, brain abscesses, onychomycosis and endocarditis have been described, with a growing interest in this type of deep mycosis on the part of mycologists and infectologists. The present paper reports descriptions of mycetism as well as infectious processes caused by basidiomycetes, such as Schizophyllum commune, Ustilago maydis (= Ustilago zeae) and Coprinus cinereus

POSSIBLE ROLE OF LUTZOMYIA MARANONENSIS AND LUTZOMYIA ROBUSTA (DIPTERA: PSYCHODIDAE) AS VECTORS OF HUMAN BARTONELLOSIS IN THREE PROVINCES OF REGION NOR ORIENTAL DEL MARAÑON, PERU

Human bartonellosis is found predominantly in Perú2, 6, 8, 12, 15, as well as in Ecuador3, 7, 10 and Colombia13, 15. In Peru, the disease is restricted to the valleys of the western-side and a few inter-andean and eastern-slopes of the andean valleys6, 15, 18 at altitudes between 1000 and 3200 masl. Most human cases are reported from the regions of Chavin, Nor Oriental del Marañon and Lima16. Lutzomyia verrucarum is presumed to be the only vector of human bartonellosis in the valleys of Peru1, 2, 8, 11, 17, 19/ Our research objetive was to detect the presence of Lu. verrucarum in various localities known to be endemic for human bartonellosis in three provinces of Region Nor Oriental del Marañon. Sandfly collections were made between 1987 and 1992 during four visits to bartonellosis-endemic provinces: San Ignacio (districts of San José de Lourdes: 1020-1260 m and La Coipa: 1200-1560 m), Jaén (districts of Santa Rosa: 1300-1680 m and Jaén: 1220-1680 m) and Utcubamba (districts of Lonya Grande: 1200 m and El Milagro: 1200-1540 m)

Coccidioidomycosis in Brazil. A case report

Coccidioidomycosis is an endemic infection with a relatively limited geographic distribution: Mexico, Guatemala, Honduras, Colombia, Venezuela, Bolivia, Paraguai, Argentina and the southwest of the United States. In these countries, the endemic area is restricted to the semiarid desert like regions which are similar to the northeast of Brazil. Case report: The patient is a 32 year-old male, born in the state of Bahia (Northeast of Brazil) and has been living in São Paulo (Southeast) for 6 years. He was admitted at Hospital das Clínicas, at the Department of Pneumology in October 1996, with a 6 month history of progressive and productive cough, fever, malaise, chills, loss of weight, weakness and arthralgia in the small joints. Chest x-rays and computerized tomography disclosed an interstitial reticulonodular infiltrate with a cavity in the right upper lobe. The standard potassium hydroxide preparation of sputum and broncoalveolar lavage demonstrated the characteristic thickened wall spherules in various stages of development. Sabouraud dextrose agar, at 25° C and 30° C showed growth of white and cottony aerial micelium. The microscopic morphology disclosed branched hyphae characterized by thick walled, barrel shaped arthroconidia alternated with empty cells. The sorological studies with positive double immunodiffusion test, and also positive complement fixation test in 1/128 dilution confirmed the diagnosis. The patient has been treated with ketoconazole and presents a favorable clinical and radiological evolution

Paracoccidioides brasiliensis: A MYCOLOGIC AND IMMUNOCHEMICAL STUDY OF TWO STRAINS

The authors conducted a mycologic, immunochemical and molecular biology study on two strains of Paracoccidioides brasiliensis, one of them, called IBIÁ, isolated from soil in the municipality of IBIÁ (Minas Gerais) by Silva-Vergara et al. (l996,1998)20,21, and the other, BAT, cultivated from a human case of paracoccidioidomycosis in Ribeirão Preto (São Paulo/Brazil) by Freitas da Silva (l996)6. Both strains showed cotton-like (M) and yeast-like (Y) forms and were pathogenic for testicularly inoculated guinea pigs, producing granulomatous and/or suppurative orchitis. Immunochemically was demonstrated the presence of gp43 by double immunodiffusion, immunoelectrophoresis and immunoblotting.

Atypical disseminated cutaneous histoplasmosis in an immunocompetent child, caused by an "aberrant" variant of Histoplasma capsulatum var. capsulatum

A case of atypical disseminated cutaneous histoplasmosis in a five-year old, otherwise healthy child, native and resident in São Paulo metropolitan area is reported. Cutaneous lesions were clinically atypical. Histologic examination disclosed a granulomatous reaction but no fungal structures could be demonstrated by specific staining nor by immunohistochemical reaction. The fungus was isolated from biopsy material on two different occasions, confirming diagnosis of an unusual fungal infection. The fungus, originally thought to be a Sepedonium sp. due to the large sized, hyaline or brownish colored tuberculated macroconidia and to lack of dimorphism (yeast form at 37 °C) produce H and M antigens, visualized by the immunodiffusion with rabbit anti-Histoplasma capsulatum hyperimmune serum. Patient’s serum sample was non reactive with H. capsulatum antigen by immunodiffusion, counterimmunoelectrophoresis and complement fixation tests, and immunoenzymatic assay failed to detect the specific circulating antigen. This serum was tested negative by double immunodiffusion when antigen obtained from one of the isolated samples was used. Both cultures were sent to Dr. Leo Kaufman, Ph.D. (Mycoses Immunodiagnostic Laboratory, CDC-Atlanta/USA), who identified them as H. capsulatum by the exoantigen and gen-probe tests. Both clinic and mycologic characteristics of the present case were atypical, suggesting the fungus isolated is an “aberrant variant” of H. capsulatum var. capsulatum, as described by SUTTON et al. in 199719. Treatment with itraconazole 100 mg/day led to cure within 90 days

Dermatophytosis caused by Trichophyton raubitschekii. Report of the first case in São Paulo, Brazil

The authors report the first case of dermatophytosis caused by Trichophyton raubitschekii in a patient from the State of São Paulo with Tinea corporis lesions localized on the buttocks. Culture on Sabouraud-agar with cycloheximide permitted the isolation and identification of the fungus, and the diagnosis was confirmed by Dr. Lynne Sigler, University of Alberta, Canada. Systemic treatment with fluconazole, 150 mg/week for 4 weeks, in combination with topical treatment with isoconazole initially yielded favorable results, with recurrence of the lesions after the medication was discontinued. This is the fifth case of this dermatophytosis published in the Brazilian medical literature.

Onychomycosis caused by Scytalidium dimidiatum. Report of two cases. Review of the taxonomy of the synanamorph and anamorph forms of this coelomycete

The authors report two cases of onychomycosis in the dystrophic form, one of them involving an HIV-positive patient, provoked by Scytalidium dimidiatum, previously called Scytalidium lignicola. The subject is reviewed from the taxonomic viewpoint, considering the anamorph Hendersonula toruloidea as a synonym of Nattrassia mangiferae, and having Scytalidium dimidiatum as the major synanamorph. According to many mycologists, Scytalidium hyalinum may be a separate species or a hyaline mutant of Scytalidium dimidiatum. Scytalidium lignicola Pesante 1957 was considered to be the type-species of the genus by ELLIS (1971)13 and later to be a "conidial state" of Hendersonula toruloidea by the same author, today known as Nattrassia mangiferae. The microorganism lives only on the roots of certain plants (mainly Platanus and Pinus). It produces pycnidia and is not considered to be a pathogen, although it is considered as a possible emerging agent capable of provoking opportunistic fungal lesions. The importance of this topic as one of the most outstanding in fungal taxonomy, so likely to be modified over time, as well as its interest in the field of dermatologic mycology, are emphasized.

Phialemonium curvatum infection after bone marrow transplantation

We report a case of cutaneous infection caused by Phialemonium curvatum GAMS et COOKE, 1983, after bone marrow transplantation. The genus Phialemonium was created by GAMS & MCGINNIS in 1983 including three new species: Ph. obovatum, Ph. curvatum and Ph. dimorphosporum, and represents an intermediate genus between Acremonium and Phialophora. Nowadays, the genus Phialemonium is considered to be a pheoid fungus which may cause the eventual lesions observed in pheo- and hyalohyphomycosis. Species of this genus have been described as opportunistic agents in humans and animals, mainly as a result of immunosuppression. In the present case, the patient had multiple myeloma and received an allogenic bone marrow transplant from his HLA-compatible brother. Two months after transplantation, he developed purplish and painful nodular lesions on the right ankle. Some of these lesions drained spontaneously and apparently hyaline mycelial filaments were observed, whose culture was initially identified as Acremonium sp. Subsequent studies showed that the fungus was Phialemonium curvatum. The infection was treated with amphotericin B, followed by ketoconazole. The patient was submitted to surgical debridement followed by two skin grafts to repair the bloody area. The duration of the treatment was 4 months and secondary prophylaxis with ketoconazole alone was maintained for one additional month. No recurrence was observed after discontinuation of treatment. The authors comment on the pathogenicity of the genus Phialemonium.

Primary cutaneous cryptococcosis due to Cryptococcus neoformans var. gattii serotype B, in an immunocompetent patient

The authors report a male patient, a seller with no detected immunosuppression, with an extensive ulcerated skin lesion localized on the left forearm, caused by Cryptococcus neoformans var. gattii serotype B. Oral treatment with fluconazole was successful. A review of the literature showed the rarity of this localization in HIV-negative patients. In contrast, skin lesions frequently occurs in HIV-positive patients, with Cryptococcus neoformans var. neoformans serotype A predominating as the etiological agent. In this paper, the pathogenicity of C. neoformans to skin lesions in patients immunocompromised or not, is discussed, showing the efficacy of fluconazole for the treatment of these processes.

Serotype, mating type and ploidy of Cryptococcus neoformans strains isolated from patients in Brazil

Serotype, mating type and ploidy of 84 strains of Cryptococcus neoformans isolated from 61 AIDS and 23 non-AIDS patients admitted in a tertiary teaching hospital in São Paulo, Brazil were examined. Among 61 strains isolated from AIDS patients, 60 strains were var. grubii (serotype A). Only one strain was var. gattii (serotype B). No var. neoformans (serotype D) was found. Among 23 strains isolated from non-AIDS patients, 15 were var. grubii (serotype A) and the remaining 8 were var. gattii, all of which were serotype B. Seventy-three of the 75 serotype A strains were the heterothallic alpha type (MATalpha) and the remaining 2 were untypable (asexual). Most of the MATalpha strains (69/73) were haploid and the remaining 4 strains were diploid. Similarly, both of the 2 asexual strains among the 75 serotype A strains were haploid. There were no alpha-mating type (MATalpha) strains among the 84 isolates. All of the 8 var. gattii strains were serotype B and haploid. Among a total of 84 strains tested, neither serotype AD nor serotype D were found. Neither triploid nor tetraploid were found. These results suggest that the serological, sexual and ploidy characteristics in C. neoformans strains isolated from AIDS patients in São Paulo were rather simple, whereas strains isolated from non-AIDS patients presented serotype A and B with predominance of serotype A.