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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.

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.

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.

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.

Serum samples from 242 HIV-positive persons were studied for the detection of capsular polysaccharide antigen of Cryptococcus neoformans; 193 of these patients presented less than 300 CD4+ cells/microliters of blood and 49 patients had more than 300 CD4+ cells/microliters. None of them had symptoms or signs characteristic of cryptococcosis. The capsular antigen of C. neofarmans was detected by latex agglutination technique with pronase pretreatment (IMMY, Crypto-Latex Antigen Detection System, Immunomycologics Inc., OK, USA); in 61% of the samples, ELISA technique was also used (Premier, Cryptococcal Antigen, Meridian Diagnostic Inc., Cincinnati, Oh, USA). The comparative study of both methods showed that the results obtained were similar in 96.9% of the cases. The capsular antigen was detected in 13 out of 193 (6.7%) patients with less than 300 CD4+ cells/microliters. Cryptococcosis was confirmed mycologically in 3 of these 13 cases (23%) by the isolation of C. neoformans in CSF or blood cultures. Three patients, who had presented negative results of both tests for capsular antigen, suffered disseminated cryptococcosis 4 to 8 months later. The predictive diagnostic value of capsular antigen detection of C. neoformans seems to be low and we believe that it should not be done routinely in asymptomatic HIV-positive persons.

Systemic disease by Cryptococcus neoformans (C. neoformans) is a common opportunistic infection in immunodeficient patients. Cellular immunity seems to be the most important determinant of resistance. The aim of this study was to assess the effect of recombinant rat interferon gamma (IFN-gamma) in murine cryptococcosis (Balb/c mice infected by IP route with the Rivas strain of C. neoformans), evaluating survival time, macroscopic and microscopic examination of the organs, and massive seeding of brain homogenate. IFN-gamma treatment, at a daily dose of 10,000 IU, did not modify significantly these variables when mice were challenged with a high inoculum (10(7) yeasts) and treatment was delayed to 5 days after infection (median survival 21 days in control mice vs. 23 days in IFN-treated). Another set of experiments suggested that IFN-gamma treatment, at a dose of 10,000 IU/day, begun at the moment of infection could be useful (it prolonged survival from 20 to 28 days, although the difference did not achieve statistical signification). When used simultaneously with infection by 3.5 x 10(5) yeasts, IFN-gamma at 10,000 IU/day for 15 days significantly prolonged survival of mice (p = 0.004). These results suggest that, depending on the experimental conditions, IFN-gamma can improve survival of mice infected with a lethal dose of C. neoformans.

Paracoccidioidomycosis is an endemic fungal disease widely distributed throughout Latin America. The potent immunosuppressor cyclophosphamide (CY) has been used to modulate host immune response to Paracoccidioides brasiliensis in an experimental model. Inbred male Buffalo/Sim rats weighing 250-300 g were inoculated with 5 x 10(6) P. brasiliensis cells of the yeast phase form by intracardiac route. One group of animals was treated with 20 mg/kg body weight at days +4, +5, +6, +7, +11 and +12 post-infection (pi.), while a control group was infected alone. No mortality was recorded in either group. Treated rats presented: a) a decrease in granuloma size, which contained less fungal cells; b) a lack of specific antibodies up to 35 days pi., and c) a significant increase in the footpad swelling test (DTH) against paracoccidioidin. Splenic cell transfer from CY-treated P. brasiliensis-infected donors to recipients infected alone led to a significant increase in DTH response in the latter versus untreated infected controls. Likewise, in treated infected recipients transferred with untreated infected donor spleen cells, footpad swelling proved greater than in controls. Thus, it would seem that each successive suppressor T lymphocyte subset belonging to the respective cascade may be sensitive to repeated CY doses administered up to 12 days pi.. Alternatively, such CY schedule may induce the appearance of a T cell population capable of amplifying DTH response.

The aim of this study was to determine the value of blood culture as a parameter of treatment effectiveness in experimental histoplasmosis. A total of thirty five hamsters, weighing approximately 120g, were inoculated intracardially with 0.1 ml of a suspension containing 4 x 10(7) cells/ml of the yeast phase of H. capsulatum. Treatments were started one week after the infection and lasted for 3 weeks. The azoles, (itraconazole, saperconazole and fluconazole) were administered once a day by gavage, at a dose of 8 mg/kg; Amphotericin B was given intraperitoneally every other day at a dose of 6mg/kg. Blood samples (1 ml) were obtained by heart punction from the 4th day after infection and were seeded in Sabouraud honey-agar and BHI-agar. The hamsters that survived were killed one week after treatment completion and the following criteria were considered for treatment evaluation: 1) rate of spontaneous death, at the end of the experience; 2) microscopic examination of Giemsa smears from liver and spleen and 3) determination of CFU in spleen cultures. Amphotericin B was the most effective drug, with negative blood cultures at day 20, negative spleen cultures in all cases and all the animals survived until the end of the study. Fluconazole was the less effective drug, blood cultures were positive during the whole experience, spleen cultures showed a similar average of CFU when compared with the control animals and 42.8% of these animals died. Saperconazole and itraconazole showed a similar activity, with survival of all hamsters and negative blood cultures at 23 and 26 days respectively. Blood culture seems to be valuable parameter for treatments' evaluation in experimental histoplasmosis of the hamster.

The efficacy of flucytosine (5-FC) and fluconazole (FLU) association in the treatment of a murine experimental model of cryptococcosis, was evaluated. Seven groups of 10 Balb C mice each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans. Six groups were allocated to receive 5-FC (300 mg/kg) and FLU (16 mg/kg), either combined and individually, by daily gavage beginning 5 days after the infection, for 2 and 4 weeks. One group received distilled water and was used as control. The evaluation of treatments was based on: survival time; macroscopic examination of brain, lungs, liver and spleen at autopsy; presence of capsulated yeasts in microscopic examination of wet preparations of these organs and cultures of brain homogenate. 5-FC and FLU, individually or combined, significantly prolonged the survival time of the treated animals with respect to the control group (p < 0.01). Animals treated for 4 weeks survived significantly longer than those treated for 2 weeks (p < 0.01). No significant differences between the animals treated with 5-FC and FLU combined or separately were observed in the survival time and morphological parameters. The association of 5-FC and FLU does not seem to be more effective than 5-FC or FLU alone, in the treatment of this experimental model of cryptococcosis.

A comparative study of antigenicity and pathogenicity for rats of six Paracoccidioides brasiliensis strains was carried out. The antigenic capacity "in vitro" of cytoplasmic extract from each strain was determined by immunodiffusion test against 6 serum samples obtained from rats experimentally infected with Paracoccidioides brasiliensis, that had presented positive reactions with a metabolic control antigen. The cytoplasmic extracts were used at final concentration of 100 mg/ml. All of them showed 2 or 3 precipitation bands in this assay. One hundred twenty Wistar rats both sexes weighing approximately 200 g, were inoculated intracardiacally with suspensions of the yeast phase of different P. brasiliensis strains. Two concentrations containing 3 x 10(7) and 5 x 10(7) cells/ml of each isolate were prepared. The inoculated animals were divided in two groups, one was left to its spontaneous outcome and the percentages of deaths were registered and the other rats were sacrificed at 14, 28, 56 and 70 days post-infection. The following parameters were taken into account for evaluation: A) presence of macroscopic granulomas in lung, liver, spleen and kidney; B) presence of P. brasiliensis in microscopic exams of the same organs, in wet preparations and in histologic sections stained by H&E; C) culture of lung and D) immunodiffusion test using pre-mortem serum samples and the homologous antigen. The correlation between the most important parameters studied in each strain are summarized as follow: As no significant differences between the two inocula employed for each strain was observed, the before mention results are the average of those obtained with each inoculation doses.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred and seventeen patients suffering systemic mycosis and AIDS were studied during 5 years in the Muñiz Hospital of Buenos Aires City. Seventy four of them presented cryptococcosis, 39 histoplasmosis and 4 both mycoses. The following specimens were studied for the diagnosis: skin and mucous membrane scrapings, bone marrow aspirations, bronchial secretions, biopsies of different organs, cerebral spinal fluid and blood cultures. Sera were also collected for serologic tests. A total of 203 samples from patients with histoplasmosis were studied, 46.3% of them showed H. capsulatum in microscopic examinations or in cultures, skin scraping was the most sensitive diagnostic method (94.7% of positive results), followed by biopsies (80%) and bone marrow cultures (42.1%). Specific antibodies were detected in 45.4% of the patients with histoplasmosis, using 2 different antigens and 3 types of serologic reactions (complement fixation test, immunodiffusion and counterimmunoelectrophoresis). A total of 413 samples from patients with cryptococcosis were examined, 69% of them confirmed the diagnosis. The mycologic study of CSF was the most sensitive method of study, since it registered positive results in 89.5%, followed by blood cultures (61.2%), skin scrapings (42.9%), and urine cultures (41.7%). Polysaccharyde antigens from C. neoformans in organic fluids were detected in almost all the cases. The aim of this study is to compare all the suitable diagnostic methods which can be used in systemic mycosis associated with AIDS in order to find the most rapid way of diagnosis.

C. immitis inoculated rats are known to develop infection restricted to lung whereas cyclophosphamide (CY) treatment leads to widespread dissemination with considerable mortality. In this study, an attempt was made to elucidate the mechanisms involved in such behaviour. With this aim, spleen cells were transferred from infected CY-treated to infected untreated rats, achieving significant specific inhibition in footpad swelling to coccidioidin in recipients, attributable to a suppressor T cell subpopulation induced by greater fungal antigen concentration arising from widespread C. immitis dissemination in immunosuppressed animals. NK activity proved similar regardless of CY treatment. Lastly, chronically infected rats presented increased colony forming units count after several weekly doses of CY, as happens in immunosuppressed patients harbouring a previous infection.

Some epidemiological characteristics of 105 cases of cryptococcosis diagnosed in Argentina, between 1981-1990, were studied. Until 1987, the annual number of cases was 4-8. It has increased since 1988 by AIDS influence and reached 35 cases in 1990. The annual number of cases non associated with AIDS has remained in 3-7 cases. The age median of the all patients, AIDS and non AIDS associated cases was 30, 30 and 45 years old, respectively. The 20-39 years old group was the most affected and the age distribution was different in AIDS and non AIDS population. Masculine predominance was more evident in AIDS than in non AIDS associated cases. The predisposing factor was AIDS in 57 patients, another different factor in 20 and unknown in 28 cases. The indirect estimation of the percentage of AIDS cases with cryptococcosis was > or = 6.19% (57 cases in 920 HIV+) during 1981-1990 this period. Cryptococcus neoformans variety neoformans was isolated from 101 cases and the gattii variety (serotype B) from only 4. The obtained data are similar to those observed in Europe and United States.

An E.L.I.S.A. test for antibody detection, with an exo-antigen of Coccidioides immitis was standardized in 67 humans sera diluted in 1/1000, 1/2000, 1/4000 and 1/8000. Eighteen sera from mycologically proved cases of coccidioidomycosis were studied: 5 were negative and 13 were positive in some dilutions. 3/26 sera of healthy persons who presented positive skin tests with coccidioidin were positive and the other 23 sera did not have positive reactions. None of the 15 sera of healthy human exhibited positive E.L.I.S.A. Serum samples of 8 patients suffering other deep mycosis were studied, 4 of them presented cross-reactions in E.L.I.S.A. tests. E.L.I.S.A. test seems to be a useful serologic technique for antibody detection in anticomplementary serum samples or when a low concentration of antibodies should be detected. As it is very sensitive, cross-reactions with other mycoses are frequent, thus the use other more specific serologic technique together E.L.I.S.A. is recommended.

The present study was carried out in two different areas of Province of Cordoba, Argentina, where there was a suspicious of endemic mycosis. The previous data were the presence of a clinical case of pulmonary cryptococcosis in one area (Alta Gracia) and the previous findings of a high incidence of coccidioidin and cryptococcin reactors in the population of the second one (Villa Dolores). In both areas soil samples for fungi were studied and Cryptococcus neoformans was found in 2/25 samples from Alta Gracia. In Villa Dolores Coccidioides immitis was isolated in 2/40 samples, and C. neoformans in 1/40 samples. Delayed hypersensitivity test with cryptococcin was determined in the population from Alta Gracia and it was found to be 5.3%. Positive cutaneous tests with coccidioidin (33.8%) and cryptococcin (31.9%) in Villa Dolores were obtained. With these findings two endemic areas of systemic mycoses in Cordoba, Argentina were delimited.

A comparative study of the "in vitro" susceptibility of 24 Cryptococcus strains to 5 antifungal drugs (amphotericin B, 5 fluorocytosine, miconazole, itraconazole and ketoconazole), was carried out. These strains were grouped according to species, varieties and isolation's origins. The minimum inhibitory concentration (M.I.C.) was determined by the agar dilution technique in yeast nitrogen base agar with dextrose. The mean geometrical of the M.I.C. values of each group was compared with the others. The results obtained were homogeneous with the only exception of the "non neoformans" strains, in which, higher M.I.C. to 5 fluorocytosine values were detected.

Cocidioidomycosis is a systemic mycosis, endemic in arid areas of the American continent. The rat was employed as an experimental host, since it had been shown to reproduce human lesions and present a chronic course of disease with granulomas mainly restricted to lungs. Given the influence of immunosuppressive therapy on the clinical course of human coccidioidomycosis, we studied the effect of cyclophosphamide (CY) in the experimental rat model. Accordingly, animals were inoculated with 400 Coccidioides immitis arthroconidia of the Acosta strain, by intracardiacal route. As single CY doses failed to alter the course of disease, three schedules were used: A) 4 daily doses of 20 mg/kg each, prior to C. immitis inoculation; B) 4 similar daily doses after infection; and C); 6 doses of 20 mg/kg each, given from day +1 to +4 then on days +8 and +9, post infection (pi), taking day 0 as the time of fungal inoculation. The first two schedules inhibited antibody formation up to day 28 pi, without modifying cellular response to coccidioidin as measured by foodpad swelling. Initially, there was greater fungal spread than in controls receiving C. immitis alone, which proved self-limiting in the latter. In contrast, schedule C led to 55% mortality with both humoral and cellular response abrogation, accompanied by extensive C. immitis dissemination. Histology disclosed significant alterations, such as the persistence of primary infection sporangia, corresponding to the acute stage of coccidioidomycosis in the absence of granuloma development. Therefore, the observed depression in cellular immunity seems responsible for the lack of inflammatory reaction capable of restricting sporangia proliferation in tissues which, in turn, enhances pathogen spread and mortality rate.