Cyclophosphamide effect on coccidioidomycosis in the rat

Coccidioidomycosis 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 559r 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.

Experimental coccidioidomycosis in the immunosuppressed rat

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.

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

THE TREATMENT OF COCCIDIOIDOMYCOSIS

SUMMARYTherapy of coccidioidomycosis continues to evolve. For primary pulmonary disease, antifungal therapy is frequently not required while prolonged courses of antifungals are generally needed for those in whom extrathoracic disseminated has occurred. Intravenous amphotericin B should be reserved for those with severe disease. Oral triazole antifungals have had a great impact on the management of coccidioidomycosis. Both fluconazole and itraconazole at 400 mg daily have been effective for various forms of coccidioidomycosis, including meningitis, although relapse after therapy is discontinued is a problem. Individuals with suppressed cellular immunity are at increased risk for symptomatic coccidioidomycosis and they include those with HIV infection, those on immunosuppressive medications, and those who have received a solid organ transplant. Pregnant women and African-American men have been identified as two other groups who are at an increased risk for symptomatic and severe infection.

Coccidioidomycosis in armadillo hunters from the state of Ceará, Brazil

Coccidioidomycosis is a systemic mycosis with a variable clinical presentation. Misdiagnosis of coccidioidomycosis as bacterial pneumopathy leads to inappropriate prescription of antibiotics and delayed diagnosis. This report describes an outbreak among armadillo hunters in northeastern Brazil in which an initial diagnosis of bacterial pneumonia was later confirmed as coccidioidomycosis caused by Coccidioides posadasii. Thus, this mycosis should be considered as an alternative diagnosis in patients reporting symptoms of pneumonia, even if these symptoms are only presented for a short period, who are from areas considered endemic for this disease.

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

Climate and acute/subacute paracoccidioidomycosis in a hyper-endemic area in Brazil

Methods Stepwise regression of annual data was applied to model incidence, calculated based on 91 cases, from lagged variables: antecedent precipitation, air temperature, soil water storage, absolute and relative air humidity, and Southern Oscillation Index (SOI). Results Multiple regression analyses resulted in a model, which explains 49% of the incidence variance, taking into account the absolute air humidity in the year of exposure, soil water storage and SOI of the previous 2 years. Conclusions The correlations may reflect enhanced fungal growth after increase in soil water storage in the longer term and greater spore release with increase in absolute air humidity in the short term.

Fatal acute respiratory distress syndrome in a patient with paracoccidioidomycosis: first case report

Paracoccidioidomycosis is a systemic mycosis that is usually acquired early in life by inhalation of conidia which convert in the lungs into yeast forms; these in turn trigger an inflammatory process. This mycosis may appear as an acute/subacute form or a chronic, adult form. Acute/subacute presentations can be observed in children and young adults, with the reticuloendothelial system frequently involved but the lungs are usually spared or present with mild clinical or radiological alterations. Acute respiratory distress syndrome (ARDS), an extensive dysfunction of the lungs alveolar-capillary barrier has occasionally been observed in other endemic mycoses such as coccidioidomycosis, cryptococcosis, histoplasmosis and blastomycosis. We describe the first patient with acute paracoccidioidomycosis who developed fatal ARDS accompanied by multiple organ injuries. The basis of the rarity of this entity in patients with paracoccidioidomycosis, as well as the reasons that may have lead to the development of ARDS in this patient are discussed.

Epidemiologic study of bronchopulmonary mycosis in the province of cordoba, argentina

An epidemiological study for histoplasmosis coccidioidomycosis and cryptococcosis made in five areas of the province of Córdoba is presented. The data obtained showed a global positivity of 41.1% for histoplasmin 26.7% for coccidioidin and 14.1% for cryptococcin. In some areas, the Rio III basin and Traslasierra, the histoplasmosis infection indexes were much higher, 53,3% and 73.1% respectively. The index of positive skin tests with Cryptococcus antigen in Traslasierra was also very high: 31.9%.

Viability and molecular authentication of Coccidioides spp. isolates from the Instituto de Medicina Tropical de São Paulo culture collection, Brazil

Coccidioidomycosis is an emerging fungal disease in Brazil; adequate maintenance and authentication of Coccidioides isolates are essential for research into genetic diversity of the environmental organisms, as well as for understanding the human disease. Seventeen Coccidioides isolates maintained under mineral oil since 1975 in the Instituto de Medicina Tropical de São Paulo (IMTSP) culture collection, Brazil, were evaluated with respect to their viability, morphological characteristics and genetic features in order to authenticate these fungal cultures. Only five isolates were viable after almost 30 years, showing typical morphological characteristics, and sequencing analysis using Coi-F and Coi-R primers revealed 99% identity with Coccidioides genera. These five isolates were then preserved in liquid nitrogen and sterile water, and remained viable after two years of storage under these conditions, maintaining the same features.

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

Micoses sistémicas

Este trabalho teve como objetivo a análise das micoses sistémicas, no que respeita à sua identificação, morfologia dos agentes patogénicos que lhes dão origem, onde são endémicas, os sintomas que apresentam, os métodos de diagnóstico e as terapêuticas disponíveis para cada patologia. As micoses sistémicas são infeções causadas por fungos patogénicos primários que têm o trato respiratório como porta de entrada, e a partir daí podem disseminar-se por todo o organismo. Os agentes antifúngicos são usados no tratamento destas infeções, em que, no caso das infeções sistémicas, predominam o uso de cetoconazol (polieno), fluconazol e itraconazol (azóis). Existem ainda estudos que demonstram que as vacinas atenuadas podem ser usadas na profilaxia destas infeções. Com este trabalho conclui-se que as infeções fúngicas estão longe de ser extintas, uma vez que se verifica cada vez mais a existência de resistências por parte dos fungos aos fármacos, sendo o diagnóstico e a terapêutica usada dois parâmetros fundamentais para um tratamento eficaz.

Paracoccidioidomicose: centenário do primeiro relato de caso

Há 100 anos Adolpho Lutz publicava relato pioneiro de enfermidade descrita como mycose pseudococcidica, hoje paracoccidioidomicose, em que discorria sobre suas manifestações clínico-histopatológicas e micológicas. Com precisão, em abril de 1908, descreveu que O agrupamento de corpúsculos kysticos é bastante característico. Geralmente há um maior no centro e outros pequenos em redor, o que sempre me produziu a impressão de resultar de um processo de gemmação. Inaugurava-se novo campo para investigações científicas.

The deep mycoses in HIV infection

The deep mycoses are uncommon infections, usually acquired from the inhalation or ingestion of fungal spores, sometimes from the soil in areas of endemicity, such as in the Americas and south-east Asia, or from decaying vegetable matter. They are also seen in immunocompromised persons and, increasingly, in HIV-infected persons. Respiratory involvement is frequent, with granuloma formation, and mucocutaneous involvement may be seen. Oral lesions of the deep mycoses are typically chronic but non-specific, though nodular or ulcerative appearances are common. Person-to-person transmission is rare. In HIV disease, the most common orofacial involvement of deep mycoses has been in histoplasmosis, cryptococcosis, aspergillosis and zygomycosis. Diagnosis is usually confirmed by lesional biopsy although culture may also be valuable. Treatment is with amphotericin or an azole.

Fatal septic shock due to a disseminated chronic form of paracoccidioidomycosis in an aged woman

Once rare, septic shock (SS) due to disseminated fungal infections has been increasingly reported due to a growing number of immunocompromised patients, but remains rare in non-immune-compromised individuals. In paracoccidioidomycosis, it has been described in only three patients with the severe, acute form of the disease. We describe the development of a refractory, fatal septic shock due to a severe disseminated chronic form of paracoccidioidomycosis in an older woman without any other microbial insults. A striking event in the evolution of her case was the severe depletion of lymphocytes from the peripheral blood and lymphoid organs. Lymphocyte depletion due to apoptosis is described in the late phase of sepsis and can contribute both to immunosuppression and the progression of SS. The possible mechanisms involved in the induction of SS in the chronic form of paracoccidioidomycosis are discussed.