Is the production of reactive oxygen and nitrogen species by macrophages associated with better infectious control in female mice with experimentally disseminated and pulmonary mucormycosis?

Different levels of resistance against Rhizopus oryzae infection have been observed between inbred (BALB/c) and outbred (Swiss) mice and are associated with the genetic background of each mouse strain. Considering that macrophages play an important role in host resistance to Rhizopus species, we used different infectious outcomes observed in experimental mucormycosis to identify the most efficient macrophage response pattern against R. oryzae in vitro and in vivo. For this, we compared BALB/c and Swiss macrophage activity before and after intravenous or intratracheal R. oryzae infections. The production of hydrogen peroxide (H2O2) and nitric oxide (NO) was determined in cultures of peritoneal (PMΦ) or alveolar macrophages (AMΦ) challenged with heat-killed spores of R. oryzae. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) were measured to confirm our findings. Naïve PMΦ from female BALB/c mice showed increased production of H2O2, TNF-α, and IL-10 in the presence of heat-killed spores of R. oryzae. Naïve PMΦ from female Swiss mice were less responsive. Naïve AMΦ from the two strains of female mice were less reactive to heat-killed spores of R. oryzae than PMΦ. After 30 days of R. oryzae intravenous infection, lower fungal load in spleen from BALB/c mice was accompanied by higher production of H2O2 by PMΦ compared with Swiss mice. In contrast, AMΦ from BALB/c mice showed higher production of NO, TNF-α, and IL-10 after 7 days of intratracheal infection. The collective findings reveal that, independent of the female mouse strain, PMΦ is more reactive against R. oryzae upon first contact than AMΦ. In addition, increased PMΦ production of H2O2 at the end of disseminated infection is accompanied by better fungal clearance in resistant (BALB/c) mice. Our findings further the understanding of the parasite-host relationship in mucormycosis.

IFN-γ Mediated Signaling Improves Fungal Clearance in Experimental Pulmonary Mucormycosis.

We established three immunocompetent murine models of pulmonary mucormycosis to determine the involvement of the adaptive immune response in host resistance in pulmonary mucormycosis, a rapidly fatal disease caused mainly by Rhizopus spp. Immunocompetent inbred (C57BL/6, BALB/c) and outbred (Swiss) strains of mice were inoculated with R. oryzae via the intratracheal route. The inoculation resulted in a disseminated infection that spread to the brain, spleen, kidney, and liver. After 7 and 30 days of R. oryzae infection, BALB/c mice showed the lowest fungal load and highest production of IFN-γ and IL-2 by splenocytes. Swiss mice showed a higher fungal load 30 days p.i. and was associated with a weak development of the Th-1 profile. To confirm our findings, R. oryzae-infected IFN-γ-/- mice were evaluated after 60 days, where the mice still showed viable fungi in the lungs. This study showed, for the first time, that pulmonary mucormycosis in three widely used mouse strains resulted in an acute fungal dissemination without immunosuppression whose outcome varies according to the genetic background of the mice. We also identified the partial role of IFN-γ in the efficient elimination of R. oryzae during pulmonary infection.

Virulence Factors and Antifungal Susceptibility in Candida Species Isolated from Dermatomycosis Patients.

Dermatomycoses caused by Candida spp. are increasingly common, however there are few reports in the literature regarding their epidemiology, pathogenesis and antifungal susceptibility of these fungal pathogens. This study aimed to identify, characterize virulence and determine the antifungal susceptibility of Candida species isolated from patients with dermatomycoses. We studied a total of 45 yeast samples isolated from dermal scrapings from patients treated at a public hospital, Bauru, São Paulo, Brazil. After identification, the samples were analyzed for protease activity, phospholipase, biofilm formation and antifungal susceptibility. The most common species was Candida albicans (40%), followed by C. krusei (22.22%), C. parapsilosis complex (22.22%) and C. famata (6.67%). Regarding virulence mechanisms, 57.78% and 28.89% of the samples showed enzymatic activity for protease and phospholipase, respectively. A total of 13.33% of the samples showed secretion of both enzymes. All isolates were biofilm producers, and a higher production was observed in C. tropicalis isolates. Regarding the antifungal susceptibility test, 97.78% of the samples had the highest levels of the minimal inhibitory concentration (MIC) for terbinafine, and one C. krusei sample showed intermediate susceptibility to fluconazole. The correct identification of dermatomycosis-related microorganisms, as well as a better knowledge of their pathogenicity and susceptibility against the antifungals used in the clinic, is extremely important for an efficient preventive and therapeutic action.

Virulence factors and antifungal susceptibility in candida species isolated from dermatomycosis patients

Dermatomycoses caused by Candida spp. are increasingly common, however there are few reports in the literature regarding their epidemiology, pathogenesis and antifungal susceptibility of these fungal pathogens. This study aimed to identify, characterize virulence and determine the antifungal susceptibility of Candida species isolated from patients with dermatomycoses. We studied a total of 45 yeast samples isolated from dermal scrapings from patients treated at a public hospital, Bauru, São Paulo, Brazil. After identification, the samples were analyzed for protease activity, phospholipase, biofilm formation and antifungal susceptibility. The most common species was Candida albicans (40%), followed by C. krusei (22.22%), C. parapsilosis complex (22.22%) and C. famata (6.67%). Regarding virulence mechanisms, 57.78% and 28.89% of the samples showed enzymatic activity for protease and phospholipase, respectively. A total of 13.33% of the samples showed secretion of both enzymes. All isolates were biofilm producers, and a higher production was observed in C. tropicalis isolates. Regarding the antifungal susceptibility test, 97.78% of the samples had the highest levels of the minimal inhibitory concentration (MIC) for terbinafine, and one C. krusei sample showed intermediate susceptibility to fluconazole. The correct identification of dermatomycosis-related microorganisms, as well as a better knowledge of their pathogenicity and susceptibility against the antifungals used in the clinic, is extremely important for an efficient preventive and therapeutic action(AU).

Borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis.

We describe a case of borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis in a patient who presented at our hospital with skin lesions and joint complaints.

Borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis / Hanseníase dimorfa tuberculoide associada à histoplasmose cutânea primária

We describe a case of borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis in a patient who presented at our hospital with skin lesions and joint complaints.

Descrevemos um caso de hanseníase dimorfa tuberculoide associada à histoplasmose cutânea primária em um paciente que procurou nosso hospital com lesões dermatológicas e queixas articulares.

Onicomicoses por leveduras em hansenianos: espécies e perfis de sensibilidade ao fluconazol / Onychomycosis by yeasts disease lepral: species and profiles of sensitivity to fluconazole

A hanseníase é uma doença infecciosa crônica, onde os distúrbios sensitivos acarretam lesões ungueais distróficas, que facilitam a colonização por fungos. Este estudo teve como objetivos pesquisar e identificar leveduras nas unhas das mãos e dos pés de pacientes hansenianos com onicomicose atendidos no Instituto Lauro de Souza Lima - Bauru, SP no período de 2003 a 2007 e avaliar a sensibilidade das leveduras isoladas ao fluconazol utilizando o método E-TestR e método de microdiluição em caldo - CLSI M-27-A 2 quando a levedura fosse sensível a concentração inibitória mínimia - CIM> a 4ug/mL no método E-TestR. Estudou-se 39 pacientes sendo 30,77% (12/39) do sexo feminino com média de idade de 53,50 e 69,23% (27/39) do sexo masculino com média de idade de 60,50 anos. Foram isoladas 59 leveduras assim distruibuidas: 28,82% de Candida albicans, 22,03% de Candida tropicalis, 18,64% Candida parapsilosis, 10,17% de Rhodotorula spp, 6,79% de Candida guilliermondii, 6,79% de Candida Krusei, 3,39% Candida pseudotropicalis, 1,69% de Candida famata e 1,69% Candida glabrata. Pelo método de E-TestR, dos 17 isolados de C. albicans um foi sensível dependente da dose (SDD) a 16 ug/mL e 10 foram sensíveis com intervalo de 1,5 a 8ug/mL e CIM 90 de 8 ug/mL. Seis isolados de Rhodotorula spp foram sensíveis com intervalo de 3 a 8ug/mL e CIM 90 de 4ug/mL. Quatro isolados de C. krusei apresentaram sensível dependente da dose (SDD) no intervalo de 16 a 32ug/mL e CIM 90 de 32ug/mL. Dois isolados de C. pseudotropicalis apresentaram sensibilidade a 2ug/mL e CIM 90 de 2ug/mL. O isolado de C. glabrata e C. famata apresentaram sensível dependente da dose (SDD) a 32 ug/mL de fluconazol(64ug/mL). Neste estudo concluiu-se que C. albicans foi a levedura mais isolada em onicomicose e pelo método de E-TestR 84,74% (50/59 das leveduras foram sensíveis ao fluconazol no intervalo de 16 a 32ug/mL e pelo método de microdiluição - CLSI M-27-A 2 18,20%(5/27) das leveduras foram resistentes...