Search

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 intracardiacly 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 intraperitonealy 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. El propósito de esta investigación fue determinar el valor de los hemocultivos para juzgar la eficacia de los tratamientos en la histoplasmosis experimental. Treinta y cinco hamsters fueron inoculados por via intracardíaca con 0.1 ml de una suspensión de la fase levaduriforme del H. capsulatum equivalente a 4 x 10(7) células/ml. Los tratamientos comenzaron 1 semana después de la infección y se mantuvieron durante 3 semanas. Los compuestos azólicos, itraconazol, saperconazol y fluconazol se administraron por gastroclisis, una vez al día, a razón de 8mg/kg de peso; la anfotericina B fue aplicada por via intraperitoneal día por medio, en dosis de 6mg/kg. Se obtuvieron muestras de sangre para hemocultivo (1 ml) a partir del 4º día post-infección y se sembraron placas de agar-miel de Sabouraud y agar infusión de cerebro y corazón. Los animales que sobrevivieron fueron autopsiados y se tomaron en consideración los siguientes parámetros: 1) tasa de muertes espontáneas al finalizar la experiencia; 2) resultados de los exámenes microscópicos de extendidos de hígado y bazo teñidos com Giemsa y; 3) UFC en cultivos de bazo. La anfotericina B fue la droga más eficaz, los hemocultivos de los animales tratados fueron negativos a partir del 20º dia de tratamiento, se negativizaron los cultivos de bazo y la totalidad de los hamsters sobrevivió. El menos eficaz fue el fluconazol que no modificó los resultados de los hemocultivos y los cultivos esplénicos y se registró el 42.8% de muertes espontáneas durante el estudio. Saperconazol e itraconazol exhibieron una eficacia similar, no se observaron muertes en los animales tratados y los hemocultivos se negativizaron a los 23 y 26 dias de tratamiento respectivamente. Los hemocultivos resultaron ser útiles como criterio para evaluar la eficacia terapéutica de las drogas antifúngicas en este modelo experimental de histoplasmosis.

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

In patients with chronic paracoccidioidomycosis (n 10), levels of tumor necrosis factor alpha, interleukin10, and interleukin-2 in serum, measured by enzyme-linked immunosorbent assay (in picograms per milliliter, as mean standard error of the mean), were higher than in normal controls (n 8): 186 40 versus 40 7( P < 0.05), 203 95 versus 20 8( P 0.001), and 96.3 78.57 versus 1.19 1.19 (P 0.045), respectively. Gamma interferon and interleukin-4 levels were similar in patients and controls. Paracoccidioidomycosis, the progressive systemic mycosis caused by Paracoccidioides brasiliensis, can evolve into several clinical forms, with different degrees of cellular immunity defect. Phagocytes and lymphocytes control the dissemination of P. brasiliensis through the production of cytokines and other functions. Different regulatory pathways determine the pattern of immune response, which can be effective, resulting in the clearance of the fungus, or ineffective, allowing it to multiply in the tissues. In areas where the fungus is endemic, at least 25% of people present a positive skin test with Paracoccidioides brasiliensis antigen, but only a few develop disease, suggesting a defect restricted to the control of P. brasiliensis. Paracoccidioidomycosis is associated with lymphopenia and

Clinical cases of coccidioidomycosis are rare in Argentina and are generally found in the large arid precordilleran area of the country. This study aims to perform a retrospective review of all coccidioidomycosis cases documented in the country from 1892 to 2009, and to describe those occurring in the last 4 years. One hundred and twenty eight cases were documented in the 117 year-period. Since the original description of the disease in 1892 until 1939, only 6 cases were registered; between 1940 and 1999, 59 (6-14/10 yrs) and the remaining 63 (49% of total cases) occurred in the last decade. The median age of 34 patients registered in 2006-2009 was 31 years (range: 7-89), male/female ratio was 1.3:1 and 12 patients were immunocompromised. Twenty-six cases were confirmed by direct microscopy and/or culture whereas the remaining ones by serology. All isolates were identified as Coccidioides posadasii. Thirty patients lived in a vast geographic region with epicenter in Catamarca Valley. Between 2006 and 2009, annual disease incidence rates in Catamarca Province increased from historical values below 0.5/100,000 to 2/100,000 inhabitants. Such increase suggests an emergency of coccidioidomycosis in that region.

A histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

Coccidioidomycosis is a systemic endemic mycosis caused by two dimorphic fungi of the Coccidioides genus: Coccidioides immitis and Coccidioides posadasii. This fungal infection is only endemic in the American Continent. The majority of the epidemiological, pathogenic, clinical, mycological and therapeutical findings were obtained in the U.S.A. Coccidioidomycosis was discovered in Argentina, at the end of the XIXth century by Alejandro Posadas. In the last two decades, a new endemic zone was found in the northeast of Brazil. Several countries of the region such as Mexico, Guatemala, Honduras, Venezuela and Argentina have performed epidemiological studies which allowed a better knowledge of the endemic areas and of the clinical characteristics of this mycosis.

The efficacy of two triazoles, SCH 39304 and fluconazole, in the treatment of disseminated cryptococcosis in Wistar rats was determined. A total of 160 rats were inoculated intracardiacally with 2 x 10(5) cells of Cryptococcus neoformans. Both drugs were administered by gavage once daily, at three doses (8, 16, and 32 mg/kg/day). Two treatment schedules were followed: (i) treatment began 1 week after infection and continued for 3 weeks and (ii) prophylaxis treatment began 3 days before infection and continued an additional 3 weeks. Evaluation was based on (i) macroscopic examination of lungs, (ii) microscopic examination of brains and lungs, (iii) histopathology of brains and lungs, and (iv) determination of number of CFU in brains. The number of CFU was the best measure of activity. SCH 39304 was more active than fluconazole in both regimens, and, prophylactically, SCH 39304 was able to achieve biological cures.

This work presents clinical, microbiological and outcome data collected from 76 patients with mycetomas at the Muñiz Hospital from 1989 to 2004. Forty-nine patients were male and 27 female; the mean age was 43.4 years. The majority of the patients acquired the infection in Argentina: the most affected provinces were Santiago del Estero with 31 cases, and Chaco with 11; 8 cases came from other countries (Bolivia 6 and Paraguay 2). The mean evolution of the disease was 9.2 years. The most frequently observed sites were: feet 63 cases, ankles 3, and knees 2. Forty-eight patients had bone lesions and 5, adenomegalies. The following etiological agents were identified: Madurella grisea 29 cases, Actinomadura madurae 26, Scedosporium apiospermum 5, Nocardia brasiliensis 5, Acremonium spp. 4 (Acremonium falciforme 2, Acremonium kiliense 1, Acremonium recifei 1), Madurella mycetomatis 3, Fusarium solani 2, Nocardia asteroides 1 and Streptomyces somaliensis 1. The main drugs used in the treatments were ketoconazole and itraconazole for maduromycotic mycetomas, and cotrimoxazole associated with ciprofloxacin or amikacin for actinomycetic mycetoma. Six patients had to undergo amputation, 25 cases achieved complete clinical remission and 34 showed remarkable improvement.

The clinical and laboratory data of 22 patients with AIDS related cryptococcosis who were able to interrupt antifungal secondary prophylaxis after HAART administration, are presented. They were 14 males and 8 females, between 15 and 50 years old (X: 34 years old). All patients presented fever and severe deterioration of their general health status, and 19 exhibited a meningeal syndrome. At the start of antifungal treatment, 59% of the cases presented50 CD4+ cells/microl, the median viral burden was 134,804 RNA copies/ml and the median titer of serum cryptococcal antigen was 1/3,000. Amphotericin B by intravenous route, (0.7 mg/kg/day) or fluconazole (600 to 800 mg/day) were given as a treatment of the initial episode, up to CSF cultures negativization. Oral fluconazole (200 mg/day) or intravenous amphotericin B, 50 mg twice a week, were given as a secondary prophylaxis. The secondary prophylaxis was interrupted when the patients had received HAART for an average lapse of 19 months (6 to 36 months) and the median CD4+ cell count was 249/microl. The follow up after secondary prophylaxis discontinuation lasted for a median lapse of 22 months. These data seem to show that secondary prophylaxis is not necessary when the patient are clinically asymptomatic and the CD4+ cell counts are above 150/microl.

In the context of HIV infection, cryptococcal meningitis is the most common mycosis threatening the patient's life. We conducted a retrospective evaluation to determine the epidemiological, microbiological, immunological and clinical characteristics of disseminated cryptococcosis in 51 hospitalised HIV seropositive patients. All the individuals (n = 51) presented reactive serology for HIV (ELISA and/or Western blot) and none fulfilled strict HAART treatment, previous to the opportunistic infection. CD4+ lymphocyte T counts showed levels between 361 and 0 cells/microliter (mean = 45). All patients but one had counts lower than 100 cells/microliter. Cryptococcosis presented as unique episode in 35 patients (68.6%) and in 16 as relapse (31.3%). In all of them we detected central nervous system involvement. The induction treatment was carried out with amphotericin B (AMB), continued with maintenance therapy with fluconazole. Lethality rate was 36.7%, slightly superior among patients in relapse (40%) compared to those who presented a first episode of the mycosis (35.2%). In those individuals for whom data were available, 65.2% of blood cultures, 94.1% of CSF cultures and 79.06% of microscopic CSF examination with India ink were positive. Titers of Cryptococcus neoformans capsular antigen in CSFor = 1/1000 were found in 36.1% andor = 1/1000 in 73.6% of serum samples. In conclusion, manifestations and severity of disseminated cryptococcosis continue maintaining the characteristics of half a decade behind, in those patients who are not treated with HAART. Neurological involvement existed in all patients of this cohort. Treatment is not able to modify the parameters of mortality seen in previous communications. Diagnostic methods applied in this study are in accordance with those in the bibliography.

A prospective cohort study was carried out in patients assisted in the F. J. Muñiz Infectious Disease Hospital, with the aim of determining the effectiveness of highly active antiretroviral therapy (HAART) implemented as soon as the sputum smear microscopy became negative (1 to 3 months) in the survival improvement of HIV/AIDS related multidrug-resistant tuberculosis patients. The cohort was recruited from June 1997 to February 1999 and compared with a pre-HAART control group that consisted of 43 patients. The follow-up of the patients was terminated June 2000. A total of 48 patients who received HAART precociously were included. The mortality rate in this group was 31.2% and the survival time of deceased patients 15.8 +/- 8.5 months. The T lymphocytes CD4+ count was initially 40.1 +/- 30.2/microL, while at the end of the observation period it was 140.4 +/- 73.04/microL and 79.1% of these patients presented undetectable viral load. In the control group the overall mortality was 90.7% and the survival time of deceased patients 8.95 +/- 3.72 months. We conclude that the early anti-retroviral therapy, together with the treatment of the multidrug-resistant tuberculosis and of other AIDS associated diseases represent a useful approach to achieve a longer and better survival in these severely immunodepressed patients.

Disseminated histoplasmosis is the most serious form of the disease produced by the fungus Histoplasma capsulatum. Histoplasmosis was first described by Darling in 1906, and it is endemic in certain areas of Central and Southeastern regions of USA, and most Latin America countries, including the Pampa húmeda and Mesopotamia regions in Argentina, but in other continents it has a limited regional distribution. Lung involvement predominates in 90% of cases, but H. capsulatum may involve bone and soft tissues. Bone lesions without other signs of infection are very rare, and are often misdiagnosed as cancer. We report a case of disseminated histoplasmosis in a man with a myelodysplasia who presented a left tibial abscess, without any clinical evidence of pulmonary involvement. The patient was successfully treated with itraconazole.

Summary A study of experimental coccidioidomycosis in hamsters (Mesocricetus auratus) is presented. Two experiments were conducted on 75 animals inoculated intracardially with the mycelial form of Coccidioides immitis. The first research (experiment I) studied the kinetics of experimental disease in 15 hamsters inoculated with 300 C. immitis arthroconidia. The parameters studied were: (a) presence of macroscopic lesions in the brain, lungs, liver, spleen and kidneys; (b) microscopic identification of spherules in wet mount preparations of these specimens; (c) samples from all organs cultured at 37 °C on Sabouraud glucose agar; (d) blood cultures drawn every 24 h during the first week and subsequently every 48 h and (e) histopathological studies of all organs. The second experiment (experiment II) determined the relationship between the inoculum size and death curve in six groups of 10 animals each, which had received doses of 10, 50, 100, 150, 200 and 300 arthroconidia, respectively. On day 14 post-inoculation, all the animals underwent skin tests and 1 ml of blood was obtained by cardiac puncture to detect antibodies. Disseminated disease with persistent fungaemia developed in all the studied animals. Coccidioides immitis was recovered from all organs, with the lungs being the first to present disease. Death occurred in all groups, regardless of the dose of arthroconidia and 83.3% died between day 22 and day 28 post-infection. The use of this model is proposed for the biological standardization of antigens, the study of prophylactic measures and the ‘‘in vivo’’ evaluation of new antifungal treatments.

Summary Twenty Wistar rats were inoculated, by the intracardiac route, with 0.5 ml each of a yeast phase suspension of Paracoccidioides brasiliensis Utero strain. The rats were sacrificed at regular intervals post-infection, at which time their lungs, heart, liver, spleen and kidneys were removed, fixed and stained for study. The parameters of interest for the lung specimens were: (a) extent of the lesions; (b) number of fungi; (c) presence of a lymphomononuclear halo. Extrapulmonary lesions were also sought. Until the fourth month post-infection, the lesions were progressive in nature, contained great numbers of viable fungi, and were surrounded by an important lymphomononuclear halo which tended to be confluent. At four and a half months p.i., the extent of the pulmonary lesions was reduced, the granulomas were less compact with fewer viable fungi, macrophages showed microvacuolation, and the lymphomononuclear halo was less pronounced. Extrapulmonary lesions, which were frequently identified in the first months post-infection, diminished from the seventh month onwards. The histological characteristics of extrapulmonary lesions were always the same as those found in the lungs. Infection tended to be controlled by the animals from the fourth month, but without complete resolution of the lesions.

Histoplasmosis is a fungal disease caused by the dimorphous fungus Histoplasma capsulatum (Hc). Cyclophosphamide (Cy) was used as an immunomodulator capable of modifying the course of the disease, as well as of regulating the mechanisms involved in T-lymphocyte mediated immune response. Rats were subjected to intracardiac inoculation of Hc followed by a fractionated treatment with a 100 mg/kg body weight dose of Cy on days +4, +5, +6, +7 and +11 pi. Until day 26 pi, treatment with Cy caused 85% mortality whereas no mortality was observed among animals only inoculated with Hc. On day 14 pi, the group of Hc animals showed a delayed hypersensitivity test (DH) of 26.60 + 13.96 as determined by the swelling of the leg. Conversely, DH was significantly depressed in rats inoculated with Hc and treated with Cy: 3.88 +/- 1.00 (p0.01). Colony forming units count in this group was 2020 CFU/g of spleen, and 24 CFU/g of spleen (p0.01) in controls. A macroscopic study of the organs revealed that the animals in the Hc+Cy group had spleenomegaly and lungs with granuloma and hemorrhagic spots. The controls only presented small lung abscesses. These findings lead to the conclusion that Cy causes a deterioration of cell mediated immune response which results in the manifestation of an acute, fatal experimental mycosis.

A case of cutaneous hyalohyphomycosis, due to Fusarium oxysporum, in a 40 years old man is presented. The patient came from Paraguay where he worked in a tropical rural area. His disease had begun 2 months before his admission as a skin ulcer located in the left leg. Clinical characteristics, diagnosis methods, differential diagnosis with other ulcers of the legs in tropical areas as well as therapeutic measures are discussed in this presentation.

Some epidemiologic, diagnostic and immunologic aspects of 93 (75 males and 18 women) cases of cryptococcosis (CRY) associated with AIDS, hospitalized in the Muñiz Hospital (MH) in Buenos Aires during 1994, were retrospectively studied. The median age (MA) of the patients under study was 28 years (17-49 y); 30 (17-49) y for males and 23 (22-34) y for women. Intravenous drug addiction (34% of patients) and homo/bisexuality in men (17%) were the most frequent risk factors for HIV infection. The MA of these groups were 27.5 (17-41) y and 34 (25-41) y, respectively. Microscopic CSF examination with India ink and the blood cultures (lysis-centrifugation) achieved the diagnosis of CRY in 67 (72%) and 16 (17%) patients, respectively. At diagnosis, the median titers for Cryptococcus neoformans capsular antigen were 1/1,000, 1/100 and 1/1 in serum, CSF and urine, respectively. Sixty five strains of C. neoformans were insolated from clinical samples; all were identified at variety neoformans employing the culture medium proposed by SalkinHurd and the D-proline assimilation test. At diagnosis, CD4+ lymphocytes counts were50/microliter in 46 patients (83.63%), and were between 51 and 200/microliter in 9 (16.4%). The CD4+/CD8+ ratio was1 in all patients. Most patients were born (83%) and lived at diagnosis (96%) in Buenos Aires (Bs As) city, Bs As outskirts towns and cities located in Bs As province.

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 HE; 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.

A urease negative strain of Cryptococcus neoformans was isolated form a patient with AIDS. The identification of the yeast was confirmed by physiological and pathogenicity tests. Clinically, the disseminated cryptococcal infection in our patient was identical to those reported in other patients with AIDS.

Twenty-seven patients suffering AIDS and disseminated histoplasmosis were included in this study, comprising twenty-three males and four females, from 18 to 46 years of age (mean = 32.9). The most frequent clinical manifestations were fever, weight loss, anaemia, skin lesions, pulmonary micronodules, hepatosplenomegaly and adenomegalies. All of them presented other infectious diseases or neoplasias frequently found in AIDS patients. The diagnosis of histoplasmosis was based upon the finding of Histoplasma capsulatum in microscopic examination or in cultures from the following specimens: skin scrapings, bone marrow aspiration, bronchoalveolar lavage, blood cultures, buccal biopsies and lymph node biopsy. Serologic reactions, searching for antibodies, were positive in 11 cases. Itraconazole by oral route, at a daily dose of 200 mg (24 cases) or 400 mg (3 cases), was administered for 6 months. Those patients who were clinically cured after receiving this scheme of treatment were treated with itraconazole 100 mg day-1 as a suppressive therapy. Twenty-three patients were considered responders, 1 as a non-responder and 3 non-assessable. The average survival time was 7.8 months and eleven cases are still alive. Itraconazole proved to be a useful medication in disseminated histoplasmosis associated with AIDS and it was very well tolerated.

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 wasor = 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.

Eighty-eight immunocompetent patients with deep mycoses from eight countries were evaluated with the same protocol for efficacy of fluconazole monotherapy. Entry doses were raised from 100 to 400 mg as safety was shown in initial cohorts, and dosages up to 2,400 mg daily and durations up to 44 months were studied. Results were very similar in different countries. Twenty-seven of 28 evaluable patients with paracoccidioidomycosis, 13 of 19 with sporotrichosis, 14 of 16 with coccidioidomycosis, and eight of eight with histoplasmosis demonstrated objective responses to therapy, as did one patient each with zygomycosis and alternariosis. For these patients, relapses have been unusual thus far. In contrast, one patient with chromoblastomycosis responded but relapsed, and six did not respond; one patient with mycetoma responded but relapsed, and two did not respond. The drug was well tolerated by patients, including six who received intravenous therapy. In vitro susceptibility tests suggested that clinical response was correlated with susceptibility but that resistance did not preclude clinical response. Fluconazole therapy appears efficacious for several deep mycoses; dosages of greater than 200 mg daily may be needed for some diseases. The further evaluation of fluconazole for these entities is warranted.

Male guinea-pigs were inoculated by the testicular route with a suspension of chlamydo-arthrospores of the filamentous phase ofC. immitis. The following histopathological changes were observed: voluminous pyocytic foci as well as granulomatous mononuclear reaction was initially observed and granuloma with multinucleated giant cells were seen 20 days after the inoculation. The following changes of the microscopic aspect of the parasite were correlatively registered: the so-called primary infection type of sporangia appear in great number three days after the inoculation. This type of sporangium is characterized by its great diameter up to 98 µ, peripheral endospore formation leaving a large central vacuole which frequently contain residual protoplasm. The endospores are thin walled, polyhedral and get free through an ostiole. Sporangia completely filled with globose endospores (the cystic type of sporangia) with radiate acidophilic formations on the peridial wall were observed in the testicles of the guinea-pigs killed 6 days after the inoculation. Reduction in number and in the size of the parasite were seen after the 20th. day of the inoculation. Radiate formation of the cell wall of the parasite appeared simultaneously with precipitin antibodies and would be the expression of antigen-antibody reaction.

Ketoconazole was administered orally in daily doses of 200 mg to 70 patients with onychomycosis. Complete recovery was attained by 48 patients, improvement of > 50% by 10 patients, and for three patients therapy failed. For the remaining nine patients the results could not be evaluated. The average duration of treatment was 7.5 months for disease due to Trichophyton species and 6.5 months for disease due to Candida species. There were no adverse effects or signs of toxicity attributable to the administration of ketoconazole. It is concluded that ketoconazole is a positive development in the effort to control the difficult problems presented by onychomycosis.

329 adult patients with tinea pedis interdigitalis, which clinical diagnosis was confirmed by positive direct microscopic examinations and cultures of organisms from the lesions, were enrolled in this open and multicentric study. Informed consent was requested and obtained in each case. The bifonazole, 1% gel, tested was applied topically once daily for 3 weeks. Weekly clinical controls were performed during the treatment period and, at least, two clinical mycological posttreatment assessments were carried out. The evaluation criteria were based on the clinical and mycological findings at the end of the second posttreatment week. According to these criteria, the results obtained were: very good (clinical cure, negative mycology) 276 (84.0%); good (clinical improvement, negative mycology) 32 (9.5%); moderate (clinical improvement, positive mycology) 20 (6.0%), and failure (no clinical and mycological changes) 1 (0.5%). Tolerance was excellent, side effects were not observed in any case.

With the objectives of determining the effectiveness of bifonazole 1% powder in the prophylactic treatment of tinea pedis interdigitalis and its local tolerance, 200 patients who achieved clinical and mycological cure in another previous trial with bifonazole 1% gel, and who were also reliable in the compliance of the treatment, were included in this study. Informed consent was requested and obtained in each case. This was a multicenter, double-blind, controlled and comparative study of one group (100 patients) treated with bifonazole verum against another group (100 patients) treated with bifonazole placebo. The allocation to each group was performed by randomization. Bifonazole was applied once daily in the morning on both feet, after showering, and inside shoes; patients applied it again when changing shoes or socks during the day. Treatment lasted up to 6 months. During the treatment, patients were clinically and mycologically assessed once a month and, if it was necessary, when signs and/or symptoms of infection reappeared. The evaluation criteria were based on the reinfection, clinically and mycologically demonstrable, during the treatment. 29 patients abandoned the treatment. Reinfection was observed in 57 out of the 171 patients who finished the treatment, 47 reinfections occurred in the placebo group and the remaining 10 in the verum group. Tolerance was excellent, no side effects were observed in any patient.

A non-comparative open trial with itraconazole in progressive forms of human histoplasmosis was carried out. Thirty two patients who completed 6 months of treatment were included; 29 suffered the chronic disseminated form; 2 exhibited a chronic pulmonary histoplasmosis and one patient presented a subacute disseminated form. Thirty patients were males and 2 females; their ages ranged from 37 to 78 years old (average 56.9). The following underlying diseases were registered: hepatopathies: 12 cases; endocrinopathies and steroid therapy: 13 cases; chronic obstructive pulmonary disease: 10 patients; malignancies: 3 cases; long treatment with psychotropic drugs; 2 cases and 1 immunodeficiency of unknown origin. The therapeutic schedule applied was: 100 mg/day, orally, during 2 months, followed by 50 mg/day for another four months. Twenty-nine patients achieved clinical cure, two showed a striking improvement (both had the chronic pulmonary form) and the treatment could not be evaluated in 1 case. A follow-up of longer than a year was registered in 23 cases, one died as a consequence of mesothelioma and another due to renal impairment, and no relapses were observed. A decreasing complement fixation titer (of more than 2-fold) was observed in 19 cases; 8 of 10 patients with negative skin tests turned positive and the erythrocyte sedimentation rate was reduced to more than a half in 24 cases. Concerning side-effects, a mild, transient and asymptomatic rise of the hepatic enzymes was registered in 9 patients. It seems that itraconazole will be the drug of choice in the treatment of human histoplasmosis in immunocompetent patients.

An open, multicentre study was carried out in 103 patients with confirmed dermatophyte infections (tinea cruris or tinea corporis). The fungi isolated were Tr. rubrum (45), Tr. mentagrophytes (11), Ep. floccosum (26) and M. canis (21). All patients were treated with a single daily application of bifonazole (1% gel) and the duration of treatment was 3 weeks. Weekly clinical controls were performed during the therapeutic period and at least two clinical and mycological examinations were given after the end of treatment. Treatment was evaluated according to the clinical and mycological findings at the 14th post-therapeutic day. The results obtained were classified as very good in 80 patients, good in 11, moderate in 11 and failure in 1 patient. Local tolerance was very good and no side-effects were observed in any patients.

Twenty-five patients with paracoccidioidomycosis and 17 patients with histoplasmosis were treated with itraconazole. All patients were adults. Those with paracoccidioidomycosis exhibited the chronic disseminated form of the disease; 21 of these patients had lesions in two or more locations, and four had lesions only on the larynx or mouth. Itraconazole was administered at a daily dosage of 50 mg for six months in the majority of these cases. All infections were clinically cured or showed striking improvement. Patients with histoplasmosis had the chronic pulmonary or chronic disseminated form of the disease. A daily dose of 100 mg was administered until clinical cure was established; the dose was then changed to 50 mg until the completion of six months of treatment. Twelve infections were clinically cured; four were strikingly alleviated. The remaining patient, who discontinued treatment with itraconazole after two months, had a severe relapse and died of respiratory failure.

Results are presented of treatment with miconazole, orally and intravenously, in patients with paracoccidioidomycosis. Twenty-eight male patients aged from 34 to 66 years and exhibiting various clinical forms of the disease were studied. Twenty-five came from endemic areas in north east Argentina (Chaco, Formosa, Misiones, Corrientes and northern Santa Fe) and the remaining three from Paraguay. Twenty patients were engaged in agricultural work or at woodmills. single or multiple lesions were observed in 24 cases. Thirteen were suffering from infection of the larynx and in two of them a tracheotomy was necessary. Twenty-three showed pulmonary lesions on X-rays. Twelve had ganglionic lesions, eight had cutaneous lesions and one patient had osteoarthritis of the knee. One patient had hepatomegaly which was unrelated to chronic alcoholism. Fourteen patients had received previous treatments such as sulphonamides and amphotericin B (7 cases); sulphonamides (3), sulphonamides and the combination sulfamethoxazole + trimethoprim (3), and one patient had received all three medications. All patients had relapsed before starting miconazole therapy. Diagnosis was established by the presence of P. brasiliensis in all cases, recovered either from cutaneous or mucosal biopsy samples or from the sputum. Complement fixation tests were positive in all patients at the onset of the treatment and the immunodiffusion reactions showed precipitation bands in 27/28 patients. Skin tests with P. brasiliensis antigens proved to be positive in 18 cases and negative in 10. The erythrocyte sedimentation rate was markedly accelerated in 22 patients (greater than 20 mm in the first hour).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study between ketoconazole and itraconazole in the prophylactic and curative treatment of experimental paracoccidioidomycosis in rats and guinea pigs was carried out. Ninety seven Wistar rats were inoculated intracardiacally with the yeast-phase of P. brasiliensis with the purpose of evaluating the prophylactic treatment. Eighty one guinea pigs were injected intratesticularly with the same microorganism with the aim of studying the healing treatment. Both drugs were administered by gavage once a day. The prophylactic treatment started 3 days before the challenger inoculation and the healing treatment begun 10 days after the challenger inoculation. The animals were divided in four groups: I), control animals to which only the solvents of both drugs were administered; II), those which received ketoconazole 40 mg/kg/day; III), those treated with the same drug 80 mg/kg/day, and IV), animals treated with itraconazole 8 mg/kg/day. Seven to 30 days after starting the healing and prophylactic treatments the results were evaluated. Itraconazole seems to be as effective as ketoconazole at 5 fold lower dosage.

One hundred and twenty-one patients with tinea (pityriasis) versicolor, confirmed by pretherapeutic clinical and mycological examination, were treated with a single daily application of bifonazole (BAY h 4502) 1% gel for 2 weeks. Weekly clinical controls were performed during the treatment period and at least two clinical and mycological post-therapeutic controls were given. Overall results were very good in 98 patients, good in 15, moderate in 7 and failure in 1 patient. Local tolerance was very good; only 1 patient presented with slight erythema and pruritus during the treatment.

A comparative study among amphotericin B, 5-fluorocytosine, itraconazole and fluconazole in the treatment of experimental cryptococcosis in mice, was carried out. Seventy male Balb C mice were inoculated intraperitoneally with 10(7) cells of Cryptococcus neoformans var. neoformans. They were divided in 7 groups of 10 animals each one: 1) treated with fluconazole by gavage at a daily dose of 16 mg/kg; 2) treated with itraconazole by gavage at a daily dose of 16 mg/kg; 3) treated with 5-fluorocytosine by gavage at a daily dose of 300 mg/kg; 4) treated with amphotericin B intraperitoneally at a dose of 6 mg/kg every other day; 5) control animals receiving polietilenglicol 200 by gavage; 6) control animals receiving distilled water by gavage and 7) control animals receiving sterile distilled water by intraperitoneal route. All the treatments started 5 days after the challenge inoculation and they were given for 2 weeks. The following parameters were taken into account: survival time, macroscopic aspect of the organ after the complete autopsy, microscopic investigation of yeasts in brain, lungs, spleen and liver, histopathology studies of these organs, the colony forming units per gram and massive seeding of brain and lungs. The survival index of the different groups was the most efficient method to measure the antifungal compounds activity. Amphotericin B increased significantly the animals survival and modified the histopathologic response in the studied organs. The colony forming units and the massive seeding in brain and lung showed that this antifungal agent is unable of producing the biological cure of this experimental model.(ABSTRACT TRUNCATED AT 250 WORDS)

The case of a young male patient who consulted because of his poor oral health is reported. AIDS was suspected to exist by the dentist on account of an oral candidiasis. He was sent to a specialized center and AIDS was confirmed. Dentist must be trained in stomatology diagnosis in order to strongly cooperate with health equipment.

Sixty-one patients with superficial candidiasis, confirmed on entry by clinical examination and mycological culture, were treated with a single daily application of a 1% bifonazole gel over a period of 4 weeks. Patients were seen every week during treatment and then followed-up for 2 weeks. An overall assessment of response to treatment, based on the clinical and mycological culture findings at the 14-day follow-up visit, showed that the results were very good in 49 and moderate in 9 patients, with only 3 patients being considered as failing to respond. Local tolerance was very good, but burning was reported by 1 patient, burning and itching by 1, and ardor and irritation by one. All these side-effects occurred at the start of treatment and they subsided without interruption of bifonazole treatment.