Conhecer antes de incorporar: um retrato dos programas para alergia ao leite implementados no Brasil / Understanding before incorporating: a portrait of milk allergy programs implemented in Brazil

Este trabalho objetiva caracterizar a assistência ofertada às crianças com alergia ao leite em programas públicos, e os desafios enfrentados na sua implantação, no contexto da pré-incorporação no Sistema Único de Saúde, de três fórmulas infantis para alergia ao leite. Estudo exploratório, transversal e abordagem quantitativa. Foram avaliados 21 programas/serviços de todas as regiões brasileiras. O principal indutor da criação destes programas foi a judicialização (80,9%), e o fornecimento destas fórmulas especiais foi realizado para crianças com até 2 anos de idade. Os principais desafios para a criação e execução destes programas foram a falta de recursos humanos e financeiros, a falta da contrapartida da União, protocolo unificado para o diagnóstico (Teste de Provocação Oral), e a escolha dos tipos das fórmulas. A estratégia mais adotada para redução dos custos foi a adequação das normas e protocolos (61,9%). Não houve diferença significativa entre os programas estaduais e municipais. Este estudo apresenta uma avaliação inédita e detalhada sobre os programas, trazendo discussões que corroboram a tomada de decisões, o uso racional de recursos públicos, a melhor assistência às crianças e o fortalecimento do sistema de saúde nacional.

This paper aims to characterize the assistance offered to children with cow's milk allergy in public programs and challenges to their implementation, specifically assessing the pre-incorporation phase in the Brazilian Unified Health System of 3 formulas for infants with milk allergy. This exploratory, cross-sectional study with a quantitative approach assessed 21 programs/services from all regions of the country. The main motivation for the creation of these programs was judicialization (80.9%), and these special formulas were provided for children up to 2 years of age. The main challenges to creating and implementing these programs were a lack of human and financial resources, no counterpart federal program, no unified protocol for diagnosis (oral provocation test), and the selection of formula types. The most common strategy for reducing costs was updating norms and protocols (61.9%), which did not differ significantly between state and municipal programs. This study presents an unprecedented and detailed evaluation of the programs, raising discussion about decision-making, the rational use of public resources, better care for children, and means of strengthening of the national health system.

Molecular epidemiology of Paracoccidiodes spp. recovered from patients with paracoccidioidomycosis in a teaching hospital from Minas Gerais State of Brazil.

INTRODUCTION: Paracoccidioidomycosis (PCM) is caused by several species of the Paracoccidioides genus which can be differentiated by interspecific genetic variations, morphology and geographic distribution. Intraspecific variability correlation with clinical and epidemiological aspects of these species still remains unclear. This study aimed to sequence the loci GP43, exon 2 and ARF of 23 clinical isolates of Paracoccidioides spp. from patients in the Southeast Region of Brazil. METHODOLOGY AND MAIN FINDINGS: GenBank was used to compare the present (23) with previous described sequences (151) that included ARF and GP43. It was identified a high polymorphism rate among the 23 isolates in comparison to the other 151. Among the isolates, 22 (95.66%) were S1/P. brasiliensis and 1 (4.34%) was identified as PS2/P. americana. A total of 45 haplotypes were found as follows: 19 from S1/P. brasiliensis (13 from the present study), 15 from P. lutzii, 6 from PS2/P. americana (1 from the present study), 3 from PS3/P. restrepiensis and 2 from PS4/P. venezuelensis. Moreover, exclusive haplotypes according to clinical origin and geographical area were found. S1/P. brasiliensis (HD = 0.655 and K = 4.613) and P. lutzii (HD = 0.649 and K = 2.906) presented the highest rate of polymorphism among all species, from which 12 isolates of the present study were clustered within S1b/P. brasiliensis. The GP43 locus showed a higher variability and was found to be the main reason for the species differentiation. CONCLUSIONS: The results herein decribed show a high intraspecific genetic variability among S1/P. brasiliensis isolates and confirm the predominance of this species in the Southeast region of Brazil. The finding of exclusive haplotypes according to clinical origin and geographical area would suggest correlation between the molecular profile with the clinical form and geographic origin of patients with PCM.

Laccase Affects the Rate of Cryptococcus neoformans Nonlytic Exocytosis from Macrophages.

Nonlytic exocytosis is a process in which previously ingested microbes are expelled from host phagocytes with the concomitant survival of both cell types. This process has been observed in the interaction of Cryptococcus spp. and other fungal cells with phagocytes as distant as mammalian, bird, and fish macrophages and ameboid predators. Despite a great amount of research dedicated to unraveling this process, there are still many questions about its regulation and its final benefits for host or fungal cells. During a study to characterize the virulence attributes of Brazilian clinical isolates of C. neoformans, we observed great variability in their rates of nonlytic exocytosis and noted a correlation between this process and fungal melanin production/laccase activity. Flow cytometry experiments using melanized cells, nonmelanized cells, and lac1Δ mutants revealed that laccase has a role in the process of nonlytic exocytosis that seems to be independent of melanin production. These results identify a role for laccase in virulence, independent of its role in pigment production, that represents a new variable in the regulation of nonlytic exocytosis.IMPORTANCECryptococcus neoformans is a yeast that causes severe disease, primarily in immunosuppressed people. It has many attributes that allow it to survive and cause disease, such as a polysaccharide capsule and the dark pigment melanin produced by the laccase enzyme. Upon infection, the yeast is ingested by cells called macrophages, whose function is to kill them. Instead, these fungal cells can exit from macrophages in a process called nonlytic exocytosis. We know that this process is controlled by both host and fungal factors, only some of which are known. As part of an ongoing study, we observed that C. neoformans isolates that produce melanin faster are more-frequent targets of nonlytic exocytosis. Further experiments showed that this is probably due to higher production of laccase, because fungi lacking this enzyme are nonlytically exocytosed less often. This shows that laccase is an important signal/regulator of nonlytic exocytosis of C. neoformans from macrophages.

Genomic diversity of the human pathogen Paracoccidioides across the South American continent.

Paracoccidioidomycosis (PCM) is a life-threatening systemic mycosis widely reported in the Gran Chaco ecosystem. The disease is caused by different species from the genus Paracoccidioides, which are all endemic to South and Central America. Here, we sequenced and analyzed 31 isolates of Paracoccidioides across South America, with particular focus on isolates from Argentina and Paraguay. The de novo sequenced isolates were compared with publicly available genomes. Phylogenetics and population genomics revealed that PCM in Argentina and Paraguay is caused by three distinct Paracoccidioides genotypes, P. brasiliensis (S1a and S1b) and P. restrepiensis (PS3). P. brasiliensis S1a isolates from Argentina are frequently associated with chronic forms of the disease. Our results suggest the existence of extensive molecular polymorphism among Paracoccidioides species, and provide a framework to begin to dissect the connection between genotypic differences in the pathogen and the clinical outcomes of the disease.

Promising antifungal activity of new oxadiazole against Candida krusei.

Candida krusei is one of the most common agents of invasive candidiasis and candidemia worldwide, leading to high morbidity and mortality rates. This species has become a problem due to its intrinsic resistance and reduced susceptibility to azoles and polyenes. Moreover, the number of antifungal drugs available for candidiasis treatment is limited, demonstrating the urgent need for the discovery of novel alternative therapies. In this work, the in vivo and in vitro activities of a new oxadiazole (LMM11) were evaluated against C. krusei. The minimum inhibitory concentration ranged from 32 to 64 µg/mL with a significant reduction in the colony forming unit (CFU) count (~3 log10). LMM11 showed fungicidal effect, similar to amphotericin, reducing the viable cell number (>99.9%) in the time-kill curve. Yeast cells presented morphological alterations and inactive metabolism when treated with LMM11. This compound was also effective in decreasing C. krusei replication inside and outside macrophages. A synergistic effect between fluconazole and LMM11 was observed. In vivo treatment with the new oxadiazole led to a significant reduction in CFU (0.85 log10). Furthermore, histopathological analysis of the treated group exhibited a reduction in the inflammatory area. Taken together, these results indicate that LMM11 is a promising candidate for the development of a new antifungal agent for the treatment of infections caused by resistant Candida species such as C. krusei.

Pesquisa translacional no Brasil: temas de pesquisa e sua aderência à Agenda do SUS / Translational research in Brazil: research topics and their adherence to the SUS Agenda

RESUMO O estudo objetivou prospectar grupos e temas de pesquisa translacional no Brasil, que detenham potencial de transformar pesquisa em soluções para saúde no âmbito nacional, e avaliar se existe convergência com a Agenda de Prioridades de Pesquisa do Ministério da Saúde, a Agenda. Estudo exploratório, descritivo, realizado a partir de busca em bases de dados públicos de acesso livre. Foram localizados 64 programas/grupos, sendo 8 programas de pós-graduação, 12 programas de pesquisa e 44 grupos na área de pesquisa translacional em saúde cadastrados no Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). A maioria dos programas de pós-graduação e todos os programas de pesquisa são vinculados a Instituições Públicas da região Sudeste. A análise temática não incluiu os 20 programas de pesquisa/pós-graduação existentes. Os 44 grupos de pesquisa foram categorizados de acordo com os 14 eixos temáticos e com as 172 linhas de pesquisa da Agenda por 4 pesquisadores independentes e cegados. Os resultados mostraram a inexistência de aderência entre os temas de pesquisa desses grupos e a Agenda de prioridades do Sistema Único de Saúde (SUS). Em cenário de aumento de demanda de necessidades em saúde, a pesquisa translacional permitiria reduzir o distanciamento da pesquisa desenvolvida no Brasil com as necessidades do SUS.

ABSTRACT This study aims to prospect groups and themes of translational research in Brazil that have the potential of transforming research into solutions for health nationally. It also aims to evaluate whether or not there is convergence with the 2018 Agenda of Research Priorities of the Ministry of Health, the Agenda. This is an exploratory, descriptive study, based on a search in public databases of free access. Sixty-four programs/groups were located: eight postgraduate programs, 12 research programs, and 44 groups linked to translational health research. Most of the postgraduate programs and all research programs are linked to Public Institutions in the Southeast region. The thematic analysis did not include the 20 ongoing research/graduate programs. The 44 research groups were categorized according to the 14 thematic axes and the 172 lines of research of the Agenda lead by four independent and blinded researchers. The results showed the inexistence of adherence between the themes these groups investigate and the SUS (Unified Health System) priority Agenda. In a scenario of increasing demand for health needs, translational research could reduce distancing between the research developed in Brazil and the necessities of the SUS.

A hidden battle in the dirt: Soil amoebae interactions with Paracoccidioides spp.

Paracoccidioides spp. are thermodimorphic fungi that cause a neglected tropical disease (paracoccidioidomycosis) that is endemic to Latin America. These fungi inhabit the soil, where they live as saprophytes with no need for a mammalian host to complete their life cycle. Despite this, they developed sophisticated virulence attributes allowing them not only to survive in host tissues but also to cause disease. A hypothesis for selective pressures driving the emergence or maintenance of virulence of soil fungi is their interaction with soil predators such as amoebae and helminths. We evaluated the presence of environmental amoeboid predators in soil from armadillo burrows where Paracoccidioides had been previously detected and tested if the interaction of Paracoccidioides with amoebae selects for fungi with increased virulence. Nematodes, ciliates, and amoebae-all potential predators of fungi-grew in cultures from soil samples. Microscopical observation and ITS sequencing identified the amoebae as Acanthamoeba spp, Allovahlkampfia spelaea, and Vermamoeba vermiformis. These three amoebae efficiently ingested, killed and digested Paracoccidioides spp. yeast cells, as did laboratory adapted axenic Acanthamoeba castellanii. Sequential co-cultivation of Paracoccidioides with A. castellanii selected for phenotypical traits related to the survival of the fungus within a natural predator as well as in murine macrophages and in vivo (Galleria mellonella and mice). These changes in virulence were linked to the accumulation of cell wall alpha-glucans, polysaccharides that mask recognition of fungal molecular patterns by host pattern recognition receptors. Altogether, our results indicate that Paracoccidioides inhabits a complex environment with multiple amoeboid predators that can exert selective pressure to guide the evolution of virulence traits.

Um olhar sobre o Complexo Econômico Industrial da Saúde e a Pesquisa Translacional / A look at the Industrial Economic Health Complex and Translational Research

RESUMO O conceito do Complexo Econômico Industrial da Saúde se inter-relaciona com o conceito de Pesquisa Translacional na medida em que aproxima o desenvolvimento científico e tecnológico do sistema acadêmico produtivo à utilização do conhecimento pela sociedade. Amplia-se o conceito tradicional da 'hélice tríplice' para incluir o uso social da inovação, proporcionando resultados concretos para o setor saúde. Nesta concepção ampliada, a dimensão translacional foi privilegiada: a necessidade de formação da agenda estratégica de plataformas tecnológicas, a indução de especialização em instituições de ciência e tecnologia, a transformação de transferência de tecnologia em capacidade de inovação com resultados para acesso universal no âmbito do Sistema Único de Saúde (SUS). A Pesquisa Translacional inclui em uma mesma estratégia o conhecimento e a produção de bens e serviços necessários à saúde e ao bem-estar, assim como o acesso da sociedade a eles, articulando o contexto do desenvolvimento científico, acadêmico e industrial no País. Este trabalho procura explicitar o referencial conceitual, ou seja: reduzir a vulnerabilidade em saúde, permitindo que o conhecimento chegue ao cidadão e que marque a própria agenda de pesquisa e de inovação.

ABSTRACT The concept of the Industrial Economic Complex of Health (Ceis) interrelates with the concept of translational research as it brings the scientific and technological development of the academic-productive system closer to the use of knowledge by the society. The traditional 'triple helix' concept is extended to include the social use of innovation providing concrete results for the health sector. In this broad conception, the translational dimension was privileged: the need for formation of the strategic agenda, technological platforms, induction of specialization in science and technology institutions, transformation of technology transfer into innovation capacity with results for universal access within the Unified Health System (SUS). Translational research includes, in one single strategy, the knowledge and the production of goods and services required for health and welfare, yet making them accessible for the society, articulating the context of scientific, academic and industrial development in the country. This paper is aimed at explaining the reference concept: reducing health vulnerability, allowing knowledge to reach the citizens and setting the agenda for research and innovation.

Antifungal activity of two oxadiazole compounds for the paracoccidioidomycosis treatment.

Paracoccidioidomycosis (PCM) is a neglected disease present in Latin America with difficulty in treatment and occurrence of serious sequelae. Thus, the development of alternative therapies is imperative. In the current work, two oxadiazole compounds (LMM5 and LMM11) presented fungicidal activity against Paracoccidioides spp. The minimum inhibitory and fungicidal concentration values ranged from 1 to 32 µg/mL, and a synergic effect was observed for both compounds when combined with Amphotericin B. LMM5 and LMM11 were able to reduce CFU counts (≥2 log10) on the 5th and 7th days of time-kill curve, respectively. The fungicide effect was confirmed by fluorescence microscopy (FUN-1/FUN-2). The hippocratic screening and biochemical analysis were performed in Balb/c male mice that received a high dose of each compound, and the compounds showed no in vivo toxicity. The treatment of experimental PCM with the new oxadiazoles led to significant reduction in CFU (≥1 log10). Histopathological analysis of the groups treated exhibited control of inflammation, as well as preserved lung areas. These findings suggest that LMM5 and LMM11 are promising hits structures, opening the door for implementing new PCM therapies.

Integrin ß1 Promotes the Interaction of Murine IgG3 with Effector Cells.

Abs exert several of their effector functions by binding to cell surface receptors. For murine IgG3 (mIgG3), the identity of its receptors (and the very existence of a receptor) is still under debate, as not all mIgG3 functions can be explained by interaction with FcγRI. This implies the existence of an alternate receptor, whose identity we sought to pinpoint. We found that blockage of integrin ß1 selectively hampered binding of mIgG3 to macrophages and mIgG3-mediated phagocytosis. Manganese, an integrin activator, increased mIgG3 binding to macrophages. Blockage of FcγRI or Itgb1 inhibited binding of different mIgG3 Abs to variable extents. Our results are consistent with the notion that Itgb1 functions as part of an IgG receptor complex. Given the more ancient origin of integrins in comparison with FcγR, this observation could have far-ranging implications for our understanding of the evolution of Ab-mediated immunity as well as in immunity to microorganisms, pathogenesis of autoimmune diseases, and Ab engineering.

Parrot Genomes and the Evolution of Heightened Longevity and Cognition.

Parrots are one of the most distinct and intriguing groups of birds, with highly expanded brains [1], highly developed cognitive [2] and vocal communication [3] skills, and a long lifespan compared to other similar-sized birds [4]. Yet the genetic basis of these traits remains largely unidentified. To address this question, we have generated a high-coverage, annotated assembly of the genome of the blue-fronted Amazon (Amazona aestiva) and carried out extensive comparative analyses with 30 other avian species, including 4 additional parrots. We identified several genomic features unique to parrots, including parrot-specific novel genes and parrot-specific modifications to coding and regulatory sequences of existing genes. We also discovered genomic features under strong selection in parrots and other long-lived birds, including genes previously associated with lifespan determination as well as several hundred new candidate genes. These genes support a range of cellular functions, including telomerase activity; DNA damage repair; control of cell proliferation, cancer, and immunity; and anti-oxidative mechanisms. We also identified brain-expressed, parrot-specific paralogs with known functions in neural development or vocal-learning brain circuits. Intriguingly, parrot-specific changes in conserved regulatory sequences were overwhelmingly associated with genes that are linked to cognitive abilities and have undergone similar selection in the human lineage, suggesting convergent evolution. These findings bring novel insights into the genetics and evolution of longevity and cognition, as well as provide novel targets for exploring the mechanistic basis of these traits.

DNAhsp65 Vaccine as Therapy against Paracoccidioidomycosis.

The conventional treatment for fungal diseases usually shows long periods of therapy and the high frequency of relapses and sequels. New strategies of the treatment are necessary. We have shown that the Mycobacterium leprae HSP65 gene can be successfully used as therapy against murine Paracoccidioidomycosis (PCM). Here, we described the methodology of DNAhsp65 immunotherapy in mice infected with the dimorphic fungus Paracoccidioides brasiliensis, one of PCM agent, evaluating cytokines levels, fungal burden, and lung injury. Our results provide a new prospective on the immunotherapy of mycosis.

An Immunomodulatory Peptide Confers Protection in an Experimental Candidemia Murine Model.

Fungal Candida species are commensals present in the mammalian skin and mucous membranes. Candida spp. are capable of breaching the epithelial barrier of immunocompromised patients with neutrophil and cell-mediated immune dysfunctions and can also disseminate to multiple organs through the bloodstream. Here we examined the action of innate defense regulator 1018 (IDR-1018), a 12-amino-acid-residue peptide derived from bovine bactenecin (Bac2A): IDR-1018 showed weak antifungal and antibiofilm activity against a Candida albicans laboratory strain (ATCC 10231) and a clinical isolate (CI) (MICs of 32 and 64 µg · ml-1, respectively), while 8-fold lower concentrations led to dissolution of the fungal cells from preformed biofilms. IDR-1018 at 128 µg · ml-1 was not hemolytic when tested against murine red blood cells and also has not shown a cytotoxic effect on murine monocyte RAW 264.7 and primary murine macrophage cells at the tested concentrations. IDR-1018 modulated the cytokine profile during challenge of murine bone marrow-derived macrophages with heat-killed C. albicans (HKCA) antigens by increasing monocyte chemoattractant protein 1 (MCP-1) and interleukin-10 (IL-10) levels, while suppressing tumor necrosis factor alpha (TNF-α), IL-1ß, IL-6, and IL-12 levels. Mice treated with IDR-1018 at 10 mg · kg-1 of body weight had an increased survival rate in the candidemia model compared with phosphate-buffered saline (PBS)-treated mice, together with a diminished kidney fungal burden. Thus, IDR-1018 was able to protect against murine experimental candidemia and has the potential as an adjunctive therapy.

Altered Expression of PRKX, WNT3 and WNT16 in Human Nodular Basal Cell Carcinoma.

BACKGROUND/AIM: Nodular and superficial are the most common subtypes of basal cell carcinoma (BCC). Signaling pathways such as Hedgehog (HH) and Wingless (WNT) signaling are associated with BCC phenotypic variation. The aim of the study was to evaluate of the expression profiles of 84 genes related to the WNT and HH signaling pathways in patients with nodular and superficial BCC. MATERIALS AND METHODS: A total of 58 BCCs and 13 samples of normal skin were evaluated by quantitative real-time polymerase chain reaction (qPCR) to detect the gene-expression profile. RESULTS: qPCR array showed segregation in BCC subtypes compared to healthy skin. PRKX, WNT3 and WNT16 were significantly (p<0.05) altered: PRKX was up-regulated, and WNT3 and WNT16 were down-regulated in nodular BCC. CONCLUSION: PRKX, WNT3 and WNT16 genes, belonging to the WNT signaling pathway, are involved in the tumorigenic process of nodular BCC.

Distinct patterns of yeast cell morphology and host responses induced by representative strains of Paracoccidioides brasiliensis (Pb18) and Paracoccidioides lutzii (Pb01).

Paracoccidioidomycosis (PCM) is a systemic mycosis, widespread in Latin America. PCM is a granulomatous disease characterized by a polymorphism of lesions depending on the pathogen's virulence, the immune status of the host and its genetic susceptibility. The thermodimorphic fungus Paracoccidioides brasiliensis was considered the only etiologic agent of PCM, yet recent works have shown significant genetic diversity among different strains of P. brasiliensis. Therefore, it has been proposed for a new species within the Paracoccidioides genus, named Paracoccidioides lutzii. To better understand the fungus-host interactions elicited by strains Pb01 and Pb18 as key representatives of P. lutzii and P. brasiliensis, respectively, we carried out studies to investigate differences in morphology, induced immune response, virulence and pathology between these two Paracoccidioides species. Our results demonstrate distinct patterns of host-parasite interaction and pathology caused by Pb18 and Pb01. These results open up new fronts for NEW: clinical studies, which may result in significant consequences for the diagnosis and treatment of PCM. Considering that our results cannot be extended to all strains of both species, more studies about the virulence among Paracoccioides must be explored in the future.

SMYD2 is highly expressed in pediatric acute lymphoblastic leukemia and constitutes a bad prognostic factor.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Although several clinical characteristics can be associated with worse prognosis, more robust biological markers still remains uncovered. SMYD2, a member of SMYD protein family, regulates the activity of several proteins through methylation. In this study, we performed quantitative real time PCR to compare the expression of SMYD2 in 83 pediatric ALL patients and non-neoplastic bone marrow samples (BMS). The study revealed that SMYD2 expression is altered in ALL BMS and its high expression was correlated with a bad prognosis. Moreover, we also revealed that SMYD2 expression level significantly decreases in patients that respond to chemotherapy treatment.

Paracoccidioides lutzii sp. nov.: biological and clinical implications.

Paracoccidioides lutzii, formerly known as 'Pb01-like' strains in the P. brasiliensis complex, is proposed as a new species based on phylogenetic and comparative genomics data, recombination analysis, and morphological characteristics. Conidia of P. lutzii are elongated, different from those of P. brasiliensis. P. lutzii occurs in the central and northern regions of Brazil. Studies comparing P. brasiliensis and P. lutzii may have significant clinical consequences for the diagnosis and treatment of paracoccidioidomycosis.

Phospholipase gene expression during Paracoccidioides brasiliensis morphological transition and infection.

Phospholipase is an important virulence factor for pathogenic fungi. In this study, we demonstrate the following: (i) the Paracoccidioides brasiliensis pld gene is preferentially expressed in mycelium cells, (ii) the plb1 gene is mostly up-regulated by infection after 6 h of co-infection of MH-S cells or during BALB/c mice lung infection, (iii) during lung infection, plb1, plc and pld gene expression are significantly increased 6-48 h post-infection compared to 56 days after infection, strongly suggesting that phospholipases play a role in the early events of infection, but not during the chronic stages of pulmonary infection by P. brasiliensis.

Paracoccidioidomycosis: eco-epidemiology, taxonomy and clinical and therapeutic issues.

Acquired by inhalation of the thermal dimorphic fungi Paracoccidioides spp. conidia, paracoccidioidomycosis ranges from symptomatic to severe and potentially fatal disseminated disease. The main focus of this review is to highlight clinical aspects of paracoccidioidomycosis and, its pathogens' diversity ecology and particularities. In addition, we present strategies for therapy, including DNA vaccines and nanostructured drugs. Molecular and morphological data supported the split of the Paracoccidioides genus into two species, Paracoccidioides brasiliensis and Paracoccidioides lutzii. An acute form of the disease affects approximately 5% of cases and involves the phagocytic mononuclear system, resulting in progressive lymphadenopathy. The chronic form affects adult men and frequently involves lungs, skin and mucous membranes, lymph nodes, and adrenal glands. The clinical manifestations depend on the ability of the host to control the fungal multiplication and dissemination. The long survival time of the fungus in the host tissues allows it to evade immune responses; therefore, successful treatment often requires long-time therapy. The consensus for treatment must consider the severity of the disease and includes sulfone derivatives, amphotericin B and azoles. Novel strategies for therapy, based on DNA vaccines and nanostructured drugs are also presented and discussed in this review.