Comparison between Itraconazole and Cotrimoxazole in the Treatment of Paracoccidiodomycosis

BackgroundThere are no published reports on studies comparing itraconazole (ITC), sulfamethoxazole-trimethoprim (cotrimoxazole, CMX), and ITC followed by CMX (ITC/CMX) in the treatment of paracoccidiodomycosis. This study aimed to compare the efficacy, effectiveness, safety and time to clinical and serologic cure in paracoccidioidomycosis patients treated with ITC or CMX, the antifungal agents most widely used.MethodologyA quasi-experimental study was performed in 177 patients with a confirmed or probable diagnosis of paracoccidioidomycosis. Treatment was divided into two stages: 1) initial, which was continued until clinical cure was achieved and the erythrocyte sedimentation rate decreased to normal values; 2) complementary, which was continued until serologic cure was achieved. Medians were compared via the Mann-Whitney test, and frequencies were compared via the chi-squared test. The assessment of variables as a function of time was performed using Kaplan-Meier curves and Cox regression. The significance level was established as p <= 0.05.Principal FindingsNo difference was found in the efficacy and effectiveness of the initial treatment of 47 individuals given ITC and 130 individuals given CMX; however, the time to clinical cure was shorter in the former compared with the latter group (105 vs. 159 days; p = 0.001), specifically in patients with the chronic form. Efficacy and effectiveness of the three regimens were similar in the complementary treatment; however, the time to serologic cure was shorter when ITC (161 days) or CMX (495 days) was used compared with ITC/CMX (881 days) [p = 0.02]. The independent predictors of a shorter time to serologic cure were treatment with ITC [risk ratio = 6.61 (2.01-21.75)] or with CMX [risk ratio = 5.11 (1.91-13.67)]). The prevalence of side effects was lower with ITC (6.4%) than with CMX (20.0%; p = 0.03).ConclusionsSince ITC induced earlier clinical cure and was better tolerated than CMX, such triazole should be considered the first-choice for PCM treatment.

High frequency of Paracoccidioides brasiliensis infection in armadillos (Dasypus novemcinctus): an ecological study

The fungus Paracoccidioides brasiliensis has been isolated from nine-banded armadillos (Dasypus novemcinctus) in different regions where paracoccidiodomycosis (PCM) is endemic. The link between PCM and these animals has provided the first valuable clue in the effort to elucidate the ecological niche of P. brasiliensis. The present study was aimed at correlating P. brasiliensis infection in armadillos with local ecological features and, if possible, the presence of the fungus in the soil in the Botucatu hyperendemic area of PCM. In this region the mean temperature ranges from 14.8 to 25.8degreesC and the annual average precipitation is 1520 mm. The sites where 10 infected animals (positive group) were collected were studied and compared with the sites where five uninfected animals were found. The occurrence of the fungus in soil samples collected from the positive armadillos' burrows and foraging sites was investigated by the indirect method of animal inoculation. Environmental data from the sites of animal capture, such as temperature, rainfall, altitude, vegetation, soil composition, presence of water and proximity of urban areas, were recorded. All 37 soil samples collected from the sites had negative fungal cultures. Positive animals were found much more frequently in sites with disturbed vegetation, such as riparian forests and artificial Eucalyptus Or Pinus forests, in altitudes below 800 m, near water sources. The soil type of the sites of positive animals was mainly sandy, with medium to low concentrations of organic matter. The pH was mainly acidic at all the sites, although the concentrations of aluminum cations (H+Al) were lower at the sites where positive animals were found. Positive armadillos were also captured in sites very close to urban areas. Our data and previous studies indicate that P. brasiliensis occurs preferentially in humid and shady disturbed forests in a strong association with armadillos.

Molecular detection of Paracoccidioides brasiliensis in road-killed wild animals

Paracoccidioides brasiliensis infections have been little studied in wild and/or domestic animals, which may represent an important indicator of the presence of the pathogen in nature. Road-killed wild animals have been used for surveillance of vectors of zoonotic pathogens and may offer new opportunities for eco-epidemiological studies of paracoccidiodomycosis (PCM). The presence of P. brasiliensis infection was evaluated by Nested-PCR in tissue samples collected from 19 road-killed animals; 3 Cavia aperea (guinea pig), 5 Cerdocyon thous (crab-eating-fox), 1 Dasypus novemcinctus (nine-banded armadillo), 1 Dasypus septemcinctus (seven-banded armadillo), 2 Didelphis albiventris (white-eared opossum), 1 Eira barbara (tayra), 2 Gallictis vittata (grison), 2 Procyon cancrivorus (raccoon) and 2 Sphiggurus spinosus (porcupine). Specific P. brasiliensis amplicons were detected in (a) several organs of the two armadillos and one guinea pig, (b) the lung and liver of the porcupine, and (c) the lungs of raccoons and grisons. P. brasiliensis infection in wild animals from endemic areas might be more common than initially postulated. Molecular techniques can be used for detecting new hosts and mapping 'hot spot' areas of PCM.

Experimental paracoccidioidomycosis in hamsters (Mesocricetus auratus): Gestational interactions

Paracoccidioides brasiliensis is a dimorphic fungus presenting specific steroid hormone receptors, both in the yeast and mycelial forms and estrogen inhibits the transition from mycelium to yeast. In the acute phase, the disease occurs with equal frequency in both sexes but in adults, females are spared. Placental fungal infection has been reported, but references to fetal infection have not been confirmed. We used 78 Syrian female hamsters divided into 3 groups: GI consisted of 30 infected mated females, GII of 20 infected unmated females and GIII of 28 uninfected mated females. Animals of group I were mated 4 weeks after infection and half of them were submitted to cesarean section on day 15 after successful mating; the other half was maintained and submitted to cesarean section and sacrificed 14 weeks after infection. Half of the animals of group II were sacrificed seven weeks and the other half 14 weeks after infection. Uninfected animals of group III were treated the same as the animals of group I. The animals were infected with strain 18 of P. brasiliensis by the intracardiac route. We evaluated the disease by the volume of granulomas in different organs, number of fungi in liver and spleen and the immunologic responses [ELISA, Double Immunodifusion (DID), Delayed Hypersensitivity Skin Test (DHT) and Macrophage Migration Inhibition (MMI)]. We studied the infection through the gestation by evaluation of the abortions, morphologic and clinic examinations of the fetuses. Our results showed that the infection did not transfer to the fetus through the placenta, but the number of abortions was larger among infected females. The newborns of GI females were smaller, weighed less and showed little vitality. The disease was more severe and disseminated in infected mated females, especially in the second sacrifice 14 weeks after inoculation, when the total volume of granulomas in them (56.3 mm) was much greater than in the infected unmated females (12 mm).

Paracoccidioidomycosis: study of six cases with ocular involvement

We present 6 patients with ocular involvement due to paracoccidioidomycosis. All cases were confirmed by the finding of Paracoccidioides brasiliensis in histopathological or direct mycologic examination of material from the lesion in the eyelid or conjunctiva. In two cases the bulbar conjunctiva was also involved, in another the cornea, and still another patient developed endophthalmitis. The presence of this mutilating disease which may lead to blindness should be suspected when chronic blepharitis or palpebral ulcerated papular lesions are detected in patients from endemic areas of paracoccidioidomycosis. This etiology should also be suspected in patients with anterior and posterior uveitis after discarding the most frequent causes of this condition. © 1988 Kluwer Academic Publishers.

Use of algorithms for semi-automatic quantification of pulmonary fibrosis and emphysema

Obtaining a semi-automatic quantification of pathologies found in the lung, through images of high resolution computed tomography (HRCT), is of great importance to aid in medical diagnosis. Paraccocidioidomycosis (PCM) is a systemic disease that affects the lung and even after effective treatment leaves sequels such as pulmonary fibrosis and emphysema. It is very important to the area of tropical diseases that the lung injury be quantified more accurately. In this stud, we propose the development of algorithms in computational environment Matlab® able to objectively quantify lung diseases such as fibrosis and emphysema. The program consists in selecting the region of interest (ROI), and through the use of density masks and filters, obtaining the lesion area quantification in relation to the healthy area of the lung. The proposed method was tested on 15 exams of HRCT of patients with confirmed PCM. To prove the validity and effectiveness of the method, we used a virtual phantom, also developed in this research. © 2013 Springer-Verlag.

Receptores envolvidos na produção de citocinas e eicosanóides por monócitos e neutrófilos humanos em resposta ao Paracoccidioides brasiliensis

Pós-graduação em Doenças Tropicais - FMB

Inquérito com paracoccidiodina em cinco cidades do Estado do Acre

A paracoccidioidomicose constitui um importante problema de saúde pública na América Latina. No Brasil, essa doença é menos freqüente nas regiões Norte e Nordeste, predominando as áreas endêmicas na região Sudeste. Apesar das condições fisiográficas da região Norte favorecerem o desenvolvimento do Paracoccidioides brasiliensis, mesmo assim, os relatos de casos são escassos. Talvez, isto deva-se ao fato da pouca consideração sobre as micoses profundas entre os diagnósticos diferenciais das condições clínicas crônicas, justificadas no fato de que a região não é considerada endêmica. Com o objetivo de descrever a prevalência da paracoccidioidomicose em cinco cidades do Estado do Acre, foi realizado estudo transversal em base populacional, por meio de inquérito com a intradermorreação à paracoccidioidina. A leitura do teste intradérmico foi realizada com 24 e 48 horas, sendo considerados reatores as pessoas com endurações de 5 ou mais milímetros de diâmetro. Foram estudadas 439 pessoas e os índices de paracoccidioidomicose-infecção na leitura de 48 horas foi de 41,2%. Os achados deste estudo indicam que o P. brasiliensis causa infecção em considerável número de pessoas na área estudada e, portanto, futuros estudos clínico-epidemiológicos e micológicos devem melhor esclarecer a história natural da micose nessa região.

Papel de neutrófilos humanos no direcionamento da resposta imune adaptativa do tipo Th1 contra o Paracoccidioides brasiliensis

Pós-graduação em Doenças Tropicais - FMB

Participação das NETs (neutrophil extracellular traps) na atividade fungicida de neutrófilos humanos contra o Paracoccidioides brasiliensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Interferon-gamma production by human neutrophils upon stimulation by IL-12, IL-15 and IL-18 and challenge with Paracoccidioides brasiliensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Identificação de Neutrophil Extracellular Traps em lesões tegumentares de pacientes com Paracoccidiodomicose e análise da formação de NETs in vitro por neutrófilos humanos desafiados com Paracoccidioides brasiliensis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)