Immunotherapy for Fungal Infections

Opportunistic fungal infections are a major health problem being appointed by some studies as the fourth main cause of hospital-acquired infection in susceptible populations. The constantly growing incidences of these diseases are associated with the growing number of susceptible individuals, such as immunocompromised individuals (leukemia, AIDS, etc) and treatment-induced immunodeficiency (hematopoietic stem cell, solid organ transplant, anticancer therapy). Furthermore, other advances in medical care, patient’s long-term hospitalization and antimicrobial therapies have created several vulnerable populations to fungal infections. Currently, antifungal drug therapies are several times inefficient, and the poor outcomes are linked to difficulties in the early diagnosis of fungal infections and drug resistance among fungal pathogens. In this context, novel therapeutic approaches are welcome to stimulate efficiently the host immune response to eliminate the fungal pathogen. This chapter is intended to review advances in immunotherapy strategies for fungal infections

Carbohydrate assimilation profiles of Brazilian Candida dubliniensis isolates based on ID 32C system

The purpose of the present study was to evaluate the identification of 19 Brazilian C. dubliniensis based on the biochemical profile exhibited when tested by the commercial identification kit ID 32C (bioMerieux). Thirteen of the isolates were rigorously identified as C. dubliniensis and the remaining isolates (six) were considered as having a doubtful profile but the software also suggested that there was 83.6% of chances for them to be C. dubliniensis. As well as pointed by the literature the identification obtained by phenotypic tests should be considered presumptive for C. dubliniensis due to variability of this new species.Dezenove culturas de C. dubliniensis isoladas no Brasil, previamente identificadas através de métodos genotípicos, foram avaliadas pelo kit comercial ID 32C (bioMerieux). Treze culturas foram identificadas como C. dubliniensis, mas as demais (seis) evidenciaram perfil duvidoso, embora o software do sistema sugerisse 83,6% de chances das mesmas pertencerem à espécie C. dubliniensis. A literatura tem registrado grande variabilidade fenotípica com esta espécie e, por isto, as identificações obtidas com este sistema deverão ser consideradas como presuntivas

Identificação de Candida dubliniensis isoladas no Brasil, através do método comercial ID 32C

The purpose of the present study was to evaluate the identification of 19 Brazilian C. dubliniensis based on the biochemical profile exhibited when tested by the commercial identification kit ID 32C (bioMerieux). Thirteen of the isolates were rigorously identified as C. dubliniensis and the remaining isolates (six) were considered as having a doubtful profile but the software also suggested that there was 83.6% of chances for them to be C. dubliniensis. As well as pointed by the literature the identification obtained by phenotypic tests should be considered presumptive for C. dubliniensis due to variability of this new species.Dezenove culturas de C. dubliniensis isoladas no Brasil, previamente identificadas através de métodos genotípicos, foram avaliadas pelo kit comercial ID 32C (bioMerieux). Treze culturas foram identificadas como C. dubliniensis, mas as demais (seis) evidenciaram perfil duvidoso, embora o software do sistema sugerisse 83,6% de chances das mesmas pertencerem à espécie C. dubliniensis. A literatura tem registrado grande variabilidade fenotípica com esta espécie e, por isto, as identificações obtidas com este sistema deverão ser consideradas como presuntivas.Universidade Federal de Santa Maria Centro de Ciências da Saúde Departamento de Microbiologia e ParasitologiaUniversidade Federal do Rio Grande do SulUniversidade Federal do Rio Grande do NorteUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Atividade enzimática e hemolítica de Candida dubliniensis

Candida dubliniensis is an opportunistic yeast that has been recovered from several body sites in many populations; it is most often recovered from the oral cavities of human immunodeficiency virus-infected patients. Although extensive studies on epidemiology and phylogeny of C. dubliniensis have been performed, little is known about virulence factors such as exoenzymatic and hemolytic activities. In this study we compared proteinase, hyaluronidase, chondroitin sulphatase and hemolytic activities in 18 C. dubliniensis and 30 C. albicans strains isolated from AIDS patients. C. albicans isolates produced higher amounts of proteinase than C. dubliniensis (p ; 0.05). Hemolytic activity was affected by CaCl2; when this component was absent, we did not notice any significant difference between C. albicans and C. dubliniensis hemolytic activities. On the contrary, when we added 2.5 g% CaCl2, the hemolytic activity was reduced on C. dubliniensis and stimulated on C. albicans tested strains (p ; 0,05). Constatou-se que a atividade hemolítica foi influenciada pelo CaCl2; em sua ausência não foram observadas diferenças na atividade hemolítica das duas espécies; todavia, ao se agregar 2,5% de CaCl2, a atividade hemolítica de C. dubliniensis foi reduzida enquanto a de C. albicans, estimulada (p < 0,05)

In vitro synergisms obtained by amphotericin B and voriconazole associated with non-antifungal agents against Fusarium spp

AbstractFusarium spp is an opportunistic fungal pathogen responsible for causing invasive hyalohyphomycosis in immunocompromised patients. Due to its susceptibility pattern with a remarkable resistance to antifungal agents the treatment failures and mortality rates are high. To overcome this situation, combination therapy may be considered which must be subjected to in vitro tests.In vitro activities of amphotericin B, itraconazole, and voriconazole associated with azithromycin, ciprofloxacin, fluvastatin, ibuprofen, metronidazole, and also the combination of amphotericin B plus rifampin against 23 strains of Fusarium spp. through the checkerboard technique based on M38-A2 [Clinical and Laboratory Standards Institute (2008). Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard, 2nd ed. (CLSI document M38-A2) (ISBN 1-56238-668-9). Wayne, PA: CLSI] were evaluated.The best synergistic interactions with amphotericin B were with ibuprofen (43.5%) (FICI [fractional inhibitory concentration index] range = 0.25–2). Combinations with voriconazole showed synergism, mainly with ciprofloxacin (30.4%) (FICI range = 0.25–3) and metronidazole (30.4%) (FICI range = 0.1–4); however, all the combinations with itraconazole were indifferent. In general, antagonistic interactions were not registered.Our results showed that in vitro synergisms obtained by some combinations studied deserve attention since they were better than those showed by the antimycotic

Pythiosis in sheep from Paraná, southern Brazil

Abstract: This paper reports pythiosis in a sheep from southwestern Paraná, Brazil, confirmed by indirect ELISA (Enzime-Linked Immunosorbent Assay) and immunohistochemistry, as well as it describes the macro and microscopic injuries, in order to understand the pathogenicity. A 4-year-old ewe from a flock of 30 Santa Inês sheep, raised semi-extensively with access to a weir, showed cachexia, bilateral enlargement in nasal region, a serous and bloody secretion with a fetid odor from its nose and swollen submandibular and retropharyngeal lymph nodes. Blood collection was performed trough jugular vein puncture in order to make complete blood cell count (CBC) and to obtain serum for the subsequent serological examination. As the hematological counts were within the normal range for sheep, the animal was euthanized and submitted to necropsy. Indirect ELISA resulted positive for pythiosis. Necropsy revealed necrosis of the hard palate with a diameter of 3.5cm and extending up to the nasal cavity, forming a fistula. Submandibular and retropharyngeal lymph nodes were enlarged and edematous on section. Microscopic findings for submandibular and retropharyngeal lymph nodes consisted in moderate infiltration of eosinophils mainly in the subcapsular sinus, characterizing reactive eosinophilic lymphadenitis. The nasal cavity revealed rhinitis and oral cavity stomatitis with necro-eosinophilic and pronounced multifocal granulomatous infiltration and presence of hyphae. Hyphae found in palate and nasal cavity were positive for Pythium insidiosum by Grocott's method and immunohistochemistry, the last one considered to be confirmatory for the pathogen diagnostic. This report has an important epidemiological aspect, as it is the first case of pythiosis in sheep confirmed by serology in South Brazil and an alert of possible infection by the pathogen in floodplains

Pythium insidiosum: morphological and molecular identification of Brazilian isolates

Pythium insidiosum is an oomycete belonging to the kingdom Stramenipila and it is the etiologic agent of pythiosis. Pythiosis is a life-threatening infectious disease characterized by the development of chronic lesions on cutaneous and subcutaneous, intestinal, and bone tissues in humans and many species of animals. The identification of P. insidiosum is important in order to implement a rapid and definitive diagnosis and an effective treatment. This study reports the identification of 54 isolates of P. insidiosum of horses, dogs and sheep that presented suspicious clinical lesions of pythiosis from different regions in Brazil, by using morphological and molecular assays. Throughout the PCR it was possible to confirm the identity of all Brazilian isolates as being P. insidiosum