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Mesenchymal stromal cells (MSC) have been widely used not only for tissue regeneration but also for the treatment of various diseases; however, it has been shown that infection of MSCs by different pathogens can attenuate their intrinsic immunomodulatory properties, affecting the proliferation and differentiation of these cells. Currently, the mechanisms by which MSCs respond to pathogen invasion are poorly understood. Therefore, the objective of the present study was to determine if the infection of bone marrow-derived MSCs, with yeasts of the pathogenic fungus Histoplasma capsulatum affects the activation, differentiation and/or proliferation of the MSCs. The results indicate that MSCs have the ability to phagocytose H. capsulatum yeasts but do not exert a notable antifungal effect. On the contrary, the infection of the MSCs with this fungal pathogen not only modulates the expression of inflammatory mediators by a mechanism dependent on TLR2, TLR4 and Dectin-1 but also affects the viability and differentiation capacity of the MSCs. These findings suggest that infection of MSCs by H. capsulatum could not only affect haematopoiesis but also modulate the immune response in the infected host and, furthermore, these MSCs could provide a niche for the fungus, allowing it to persist and evade the immune response of the host.

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Background Candidiasis is one of the most frequent opportunistic infections in immunosuppressed and/or hospitalized patients. In countries like Colombia, candidiasis is associated with a mortality rate of ∼ 46%. Growing pharmacological resistance of Candida spp., and the appearance of the emerging pathogen Candida auris, have turned candidiasis into a major public health problem. Different types of antimicrobial peptides have been investigated as a therapeutic alternative to control candidiasis effectively and safely. Objective This work aimed at evaluating the in vitro antifungal activity of three synthetic antimicrobial peptides (35 409, 1609, and 29 009) obtained from Plasmodium falciparum Rif1 protein against C. auris, C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis, species with worldwide clinical importance. Methods The minimum inhibitory concentrations (MIC) of the three peptides against Candida species were determined by the plate microdilution method; the peptides’ effect on biofilm formation in C. auris and C. albicans species was also evaluated through the XTT metabolic activity assay. Additionally, the structural damages in C. auris and C. albicans caused by the action of the peptides were observed by transmission electron microscopy (TEM) and finally, the in vitro peptides’ cytotoxicity against L929 murine fibroblasts was verified. Results Our findings showed that the three peptides herein evaluated, displayed antifungal activity in both planktonic and sessile Candida cells. Likewise, the TEM evidenced morphological alterations induced by the peptides, both in the membrane and at the intracellular level of the yeasts. As well, total safety against the murine cell line L929 with 24 h of treatment was observed. Conclusions From these results, we conclude that the antimicrobial peptides 35 409, 1609, and 29 009 are potential therapeutic alternatives against the most important Candida species in Colombia and the world.

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objectives Host defense peptides (HDP) are produced by a diversity of beetles. The aims of this work were (1) to find new promising peptides from the Coleoptera family Scarabaeidae with potential biomedical applications, (2) to modify physicochemical and structural characteristics of one of the most promissory peptides in order to improve its antimicrobial properties, and (3) to evaluate the in vitro activity of the HDPs against reference strains of pathogenic Candida and Cryptococcus yeasts. Materials and Methods From the Scarabaeidae family transcriptome, 14 promising HDPs were identified. Subsequently, we designed 19 new sequences from Act8 peptide modifying the net charge, hydrophobic angle, and the general composition of amino acids, among other properties, in order to improve the HDPs antifungal activity. The in vitro antifungal susceptibility of the 33 HDPs against C. albicans SC5314, C. krusei, ATCC 6558, C. parapsilosis ATCC 22019, C. glabrata ATCC 2001, C. tropicalis ATCC 750, C. neoformans H99, and C. gattii H0058-I-2029 isolates were evaluated by broth microdilution, with a concentration ranging from 0.19 to 50 μg/ml. Results All 14 peptides identified showed in vitro activity against C. krusei, C. parapsilosis, and C. glabrata. One peptide showed in vitro activity against C. albicans, 6 against C. tropicalis, 11 against C. neoformans and 13 against C. gattii. As well the 19 modified peptides showed in vitro activity against C. krusei, C. parapsilosis, C. tropicalis, C. neoformans, and C. gattii. A total of 15 modified peptides showed in vitro activity against C. albicans, and 3 against C. glabrata. MIC ranges per species and per peptide are shown in Table 1. Conclusions The HDPs herein analyzed showed a significant in vitro antifungal activity against six Candida and two Cryptococcus pathogenic species. Our findings encourage further work with in vivo experimental models in order to better understand the action mechanisms of these antimicrobial peptides. HDPs from different species are becoming a promising therapeutic alternative in the control of fungal infections.

Histoplasma antigen detection in urine is a rapid diagnostic method for disseminated histoplasmosis, although cross-reactivity has been reported in specimens from patients with other thermally dimorphic fungal infections. We tested urine specimens, from persons with suspected invasive fungal infections, using a commercial monoclonal antibody Histoplasma enzyme immunoassay (EIA) at a South African national mycology reference laboratory from August 2014 through December 2018. Corresponding fungal culture and histopathology results were obtained from an electronic laboratory information system. In some cases, cultured fungal isolates were sent with the urine specimen for species-level identification by phenotypic and molecular methods. Cross-reactivity was confirmed using culture filtrates of several fungal pathogens. Of 212 referred cases, 41 (19%) were excluded since they had no recorded clinical history (n = 1), alternative diagnoses were confirmed (n = 2), or no fungal culture or histopathology results (n = 38). Eighty-seven of 212 (41%) had laboratory evidence of an invasive fungal disease, while 84 (40%) did not. Of the 87 cases, 37 (43%) were culture-confirmed mycoses: emergomycosis (n = 18), histoplasmosis (n = 8), sporotrichosis (n = 6), cryptococcosis (n = 2), talaromycosis (n = 1), and other fungi isolated (n = 2). The sensitivity and specificity of the EIA were calculated for two groups: culture-confirmed (n = 37) and histology-confirmed invasive fungal disease (n = 50). The sensitivity and specificity of the EIA for diagnosis of histoplasmosis compared to culture were 88% (7/8, 95%CI 47-100%) and 72% (21/29, 95%CI 53-87%), respectively, and for diagnosis of emergomycosis/histoplasmosis compared to histology was 83% (29/35, 95%CI 66-93%) and 93% (14/15, 95%CI 68-100%), respectively. Cross-reactions occurred in urine specimens of patients with Emergomyces africanus infection and in culture filtrates of E. africanus, T. marneffei and Blastomyces species. A commercial Histoplasma EIA had satisfactory accuracy for diagnosis of culture-confirmed histoplasmosis, but cross-reacted in urine specimens from patients with invasive disease caused by the closely-related pathogen, E. africanus and in culture filtrates of E. africanus and other related fungi. Lay summary Emergomyces africanus and Histoplasma capsulatum are fungi that cause a multi-system disease among HIV-seropositive persons with a low CD4 cell count. Handling live cultures of these fungi to confirm a diagnosis requires specialized laboratory equipment and infrastructure which is infrequently accessible in low-resource settings. The features of the two diseases (i.e., disseminated histoplasmosis and emergomycosis) may be indistinguishable when infected tissue is prepared, stained, and examined under a microscope. Enzyme immunoassays (EIA) have been developed as rapid diagnostic tools for the detection of a cell wall component of H. capsulatum in urine specimens, although cross-reactions have been reported in specimens from patients with other fungal infections. We evaluated the accuracy of a commercial Histoplasma EIA to diagnose histoplasmosis and to assess cross-reactions in urine specimens from persons with emergomycosis and in cultures of E. africanus and related fungi. We report a sensitivity and specificity of 88% (95%CI 47-100%) and 72% (95%CI 53-87%) for diagnosis of histoplasmosis compared to culture and 83% (95%CI 66-93%) and 93% (95%CI 68-100%) for diagnosis of either histoplasmosis/emergomycosis compared to a diagnosis made by microscopic examination of infected tissue. The assay cross-reacted in urine specimens from patients with emergomycosis and in culture filtrates of related fungi. Although the EIA cross-reacted with other related fungi, this test can decrease the time to diagnosis and facilitate early treatment of emergomycosis and histoplasmosis in South Africa.

Background: Progressive disseminated histoplasmosis (PDH) is an important cause of mortality in persons living with HIV (PLHIV), especially in countries where patients have limited access to antiretroviral therapies and diagnostic testing. Objective: A lateral flow assay (LFA) to detect Histoplasma capsulatum antigen in serum developed by MiraVista® was evaluated. Methods: We tested 75 serum samples: 24 from PLHIV and culture-proven PDH and 51 from PLHIV with other fungal and bacterial infections as well as people without HIV. LFA devices were read manually (read by eye) and by an automated reader. Results: When the LFA was read manually, sensitivity was 96% and specificity was 90%. When an automated reader was used, sensitivity was 92% and specificity was 94%. The Kappa index comparing manual and automated reader was 0.90. Cross-reactions were observed principally in samples from patients with proven diagnosis of paracoccidioidomycosis. Conclusions: The MiraVista® Diagnostics Histoplasma antigen LFA had high analytical performance and good agreement between manual and automated reader. This LFA allows Histoplasma antigen testing with minimal laboratory equipment and infrastructure requirements. © 2019 Blackwell Verlag GmbH

A total of 23/45 (51%) patients with AIDS and histoplasmosis from Medellín, Colombia had other infections. Tuberculosis was the most common (n = 16/23, 70%). Pneumocystosis and cryptococcosis were found in three patients each (13%), bacterial infection and cytomegalovirus occurred each in two patients (9%) while toxoplasmosis, herpes virus and esophageal candidiasis were recorded in one patient each (4%). Of all co-infected patients, 18/23 (78%) had one, four (17%) had two and one (4%) had three additional opportunistic infections. © 2017 The Author(s)

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs. © 2019 by the authors.

Histoplasmosis is common among persons living with human immunodeficiency virus/acquired immune deficiency syndrome (PLWHA) in Latin America, but its diagnosis is difficult and often nonspecific. We conducted prospective screening for histoplasmosis among PLWHA with signs or symptoms suggesting progressive disseminated histoplasmosis (PDH) and hospitalized in Hospital La María in Medellín, Colombia. The study's aim was to obtain a clinical and laboratory profile of PLWHA with PDH. During 3 years (May 2008 to August 2011), we identified 89 PLWHA hospitalized with symptoms suggestive of PDH, of whom 45 (51%) had histoplasmosis. We observed tuberculosis (TB) coinfection in a large proportion of patients with PDH (35%), so all analyses were performed adjusting for this coinfection and, alternatively, excluding histoplasmosis patients with TB. Results showed that the patients with PDH were more likely to have Karnofsky score ≤ 30 (prevalence ratio [PR] = 1.98, 95% confidence interval [CI] = 0.97-4.06), liver compromised with hepatomegaly and/or splenomegaly (PR = 1.77, CI = 1.03-3.06) and elevation in serum of alanine aminotransferase and aspartate aminotransferase to values > 40 mU/mL (PR = 2.06, CI = 1.09-3.88 and PR = 1.53, CI = 0.99-2.35, respectively). Using multiple correspondence analyses, we identified in patients with PDH a profile characterized by the presence of constitutional symptoms, namely weight loss and Karnofsky classification ≤ 30, gastrointestinal manifestations with alteration of liver enzymes and hepatosplenomegaly and/or splenomegaly, skin lesions, and hematological alterations. Study of the profiles is no substitute for laboratory diagnostics, but identifying clinical and laboratory indicators of PLWHAwith PDH should allow development of strategies for reducing the time to diagnosis and thus mortality caused by Histoplasma capsulatum. Copyright © 2016 by The American Society of Tropical Medicine and Hygiene.

Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria. A confirmed case of histoplasmosis was defined as a person with a positive culture or urine antigen test for Histoplasma capsulatum. Demographic and clinical data were also collected and analyzed. Of 263 enrolled as suspected cases of histoplasmosis, 101 (38.4%) were confirmed cases. Median time to diagnosis was 15 days after presentation (interquartile range [IQR] = 5-23). Crude overall mortality was 43.6%; median survival time was 19 days (IQR = 4-69). Mycobacterial infection was diagnosed in 70 (26.6%) cases; 26 (25.7%) histoplasmosis cases were coinfected with mycobacteria. High mortality and short survival time after initial symptoms were observed in patients with histoplasmosis. Mycobacterial coinfection diagnoses were frequent, highlighting the importance of pursuing diagnoses for both diseases. and copy; 2017 by The American Society of Tropical Medicine and Hygiene.

Histoplasmosis is considered one of the most important endemic and systemic mycoses worldwide. Until now few molecular techniques have been developed for its diagnosis. The aim of this study was to develop and evaluate three real time PCR (qPCR) protocols for different protein-coding genes (100-kDa, H and M antigens) using an animal model. Fresh and formalin-fixed and paraffin-embedded (FFPE) lung tissues from BALB/c mice inoculated i.n. with 2.5x106 Histoplasma capsulatum yeast or PBS were obtained at 1, 2, 3, 4, 8, 12 and 16 weeks post-infection. A collection of DNA from cultures representing different clades of H. capsulatum (30 strains) and other medically relevant pathogens (36 strains of related fungi and Mycobacterium tuberculosis) were used to analyze sensitivity and specificity. Analytical sensitivity and specificity were 100% when DNAs from the different strains were tested. The highest fungal burden occurred at first week post-infection and complete fungal clearance was observed after the third week; similar results were obtained when the presence of H. capsulatum yeast cells was demonstrated in histopathological analysis. In the first week post-infection, all fresh and FFPE lung tissues from H. capsulatum-infected animals were positive for the qPCR protocols tested except for the M antigen protocol, which gave variable results when fresh lung tissue samples were analyzed. In the second week, all qPCR protocols showed variable results for both fresh and FFPE tissues. Samples from the infected mice at the remaining times post-infection and uninfected mice (controls) were negative for all protocols. Good agreement was observed between CFUs, histopathological analysis and qPCR results for the 100-kDa and H antigen protocols. We successfully standardized and validated three qPCR assays for detecting H. capsulatum DNA in fresh and FFPE tissues, and conclude that the 100-kDa and H antigen molecular assays are promising tests for diagnosing this mycosis. © This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Next-generation technologies and bioinformatics enabled source attribution and implementation of effective control strategies., We used whole-genome sequence typing (WGST) to investigate an outbreak of Sarocladium kiliense bloodstream infections (BSI) associated with receipt of contaminated antinausea medication among oncology patients in Colombia and Chile during 2013–2014. Twenty-five outbreak isolates (18 from patients and 7 from medication vials) and 11 control isolates unrelated to this outbreak were subjected to WGST to elucidate a source of infection. All outbreak isolates were nearly indistinguishable (21,000 single-nucleotide polymorphisms were identified from unrelated control isolates, suggesting a point source for this outbreak. S. kiliense has been previously implicated in healthcare-related infections; however, the lack of available typing methods has precluded the ability to substantiate point sources. WGST for outbreak investigation caused by eukaryotic pathogens without reference genomes or existing genotyping methods enables accurate source identification to guide implementation of appropriate control and prevention measures.

Background Histoplasma capsulatum comprises a worldwide complex of saprobiotic fungi mainly found in nitrogen/phosphate (often bird guano) enriched soils. The microconidia of Histoplasma species may be inhaled by mammalian hosts, and is followed by a rapid conversion to yeast that can persist in host tissues causing histoplasmosis, a deep pulmonary/systemic mycosis. Histoplasma capsulatum sensu lato is a complex of at least eight clades geographically distributed as follows: Australia, Netherlands, Eurasia, North American classes 1 and 2 (NAm 1 and NAm 2), Latin American groups A and B (LAm A and LAm B) and Africa. With the exception of the Eurasian cluster, those clades are considered phylogenetic species. Methodology/Principal Findings Increased Histoplasma sampling (n = 234) resulted in the revision of the phylogenetic distribution and population structure using 1,563 aligned nucleotides from four protein-coding regions. The LAm B clade appears to be divided into at least two highly supported clades, which are geographically restricted to either Colombia/Argentina or Brazil respectively. Moreover, a complex population genetic structure was identified within LAm A clade supporting multiple monophylogenetic species, which could be driven by rapid host or environmental adaptation (~0.5 MYA). We found two divergent clades, which include Latin American isolates (newly named as LAm A1 and LAm A2), harboring a cryptic cluster in association with bats. Conclusions/Significance At least six new phylogenetic species are proposed in the Histoplasma species complex supported by different phylogenetic and population genetics methods, comprising LAm A1, LAm A2, LAm B1, LAm B2, RJ and BAC-1 phylogenetic species. The genetic isolation of Histoplasma could be a result of differential dispersion potential of naturally infected bats and other mammals. In addition, the present study guides isolate selection for future population genomics and genome wide association studies in this important pathogen complex., Author Summary Histoplasmosis is a potentially severe fungal disease of mammals caused by Histoplasma capsulatum. The highest incidence of the disease is reported on the American continent, and approximately 30% of HIV and histoplasmosis co-infections are fatal. Previous studies have suggested at least 7 phylogenetic species within H. capsulatum, however by increasing taxon sampling and using different phylogenetic and population genetic methods, we detect at least 5 additional phylogenetic species within Latin America (LAm A1, LAm A2, LAm B1, LAm B2, RJ and BAC-1). These phylogenetic species are nested in the former LAm A clade. We found evidence that bats may be a cause of speciation in Histoplasma, as well-supported monophyletic clades were found in association with different species of bats. The radiation of the Latin American H. capsulatum species took a place around 5 million years ago, which is consistent with the radiation and diversification of bat species. Previous phylogenetic distribution of Histoplasma is upheld and strong support is indicated for the species delineation and evolution of this important pathogen.

RESUMEN: La candidiasis invasora representa el 75% de las infecciones por hongos en pacientes hospitalizados, con una mortalidad que alcanza cifras hasta del 78%. La frecuencia de estas infecciones varía de acuerdo con el servicio de hospitalización y los factores de riesgo de los pacientes. Paralelamente, se han venido observando cambios en la epidemiología de las especies de Candida, variaciones en su prevalencia y en la resistencia a los antimicóticos según su localización geográfica. Por todo lo anterior, es imperativo establecer un diagnóstico temprano que lleve a la identificación correcta de la especie implicada de manera que se instaure un pronto y adecuado tratamiento antimicótico. El diagnóstico de la candidiasis invasora continúa siendo un reto, en el cual combinar los diferentes métodos diagnósticos, los microbiológicos, los inmunológicos y los nuevos moleculares, aún en desarrollo y validación, es la mejor estrategia para lograr un dictamen oportuno. En esta revisión se describen los métodos disponibles, sus limitaciones y las perspectivas de los que están en etapa de desarrollo y validación. En la última década se cuenta con métodos de referencia para la medición de susceptibilidad in vitro a los antimicóticos, lo cual ha permitido conocer los perfiles de sensibilidad de las diferentes especies de Candida a escala mundial y local. ABSTRACT: Invasive candidiasis represents 75% of fungal infections in hospitalized patients, with reported mortalities up to 78%. The frequency of these infections varies according to the hospital services and the risk factors of the patients. In parallel, changes in the epidemiology of the Candida species have been observed, in particular variations in their prevalence and in their resistance to antifungals according to geographic location. For these reasons it is crucial to establish an early diagnosis that identifies the pathogen to the species level in order to allow an appropriate therapeutic decision. The diagnosis of invasive candidiasis continues to be a challenge, where combining the different available methods (microbiologic, immunologic and new molecular approaches) is the best strategy to achieve a prompt and accurate diagnosis. We review the currently available assays for conventional and molecular diagnosis, their limitations, and the perspectives for assays that are now in development and validation. In the last decade, well established reference methods have become available for testing antifungal susceptibility and this has allowed worldwide and regional sensitivity profiles to be established for the different Candida species. COL0013709

Histoplasmosis causes a significant mortality, especially persons living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) from developing countries where access to both appropriate diagnostic methods and antiretroviral therapy are limited. A total of 81 physicians assigned to 17 Colombian departments (states) received training in the clinical, epidemiological, and diagnostic aspects of histoplasmosis. Once this training was received and during the period of October 2009-November 2012, these physicians sent biological samples for immunodiagnostic, mycological, and molecular tests from their patients with suspicion of histoplasmosis. A total of 1,536 samples from 768 patients were evaluated. Of the 768 patients studied, 463 (60%) were HIV positive, 214 (28%) HIV negative, and in 91 (12%) this diagnosis was unknown, and 538 (70%) were males. The 1,536 specimens studied comprised 722 sera, 439 blood samples, and 241 urines, which were tested by immunodiffusion (ID), culture, and antigenuria, respectively; in addition, 134 specimens were tested by performing a molecular assay. Histoplasmosis was diagnosed in 133 patients (17%). After the training, we observed more diagnoses from 27 to 44 cases per year. In this study, a significantly increased number of histoplasmosis cases reported by year were observed after implementing an educational training program. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene.

Microorganisms adhere to extracellular matrix proteins by means of their own surface molecules. Paracoccidioides brasiliensis conidia have been shown to be capable of interacting with extracellular matrix proteins. We aimed at determining the presence of fungal proteins that could interact with extracellular matrix protein and, if found, attempt their purification and characterization. Various extracts were prepared from P. brasiliensis mycelial and yeast cultures (total homogenates, β-mercaptoethanol, and sodium dodecyl sulfate [SDS] extracts) and analyzed by ligand affinity assays with fibronectin, fibrinogen and laminin. Two polypeptides were detected in both fungal forms. SDS extracts that interacted with all the extracellular matrix protein were tested; their molecular masses were 19 and 32 kDa. Analysis of the N-terminal amino acid sequence of the purified 32-kDa mycelial protein showed substantial homology with P. brasiliensis , Histoplasma capsulatum , and Neurospora crassa hypothetical proteins. Additionally, a monoclonal antibody (MAb) produced against this protein recognized the 32-kDa protein in the SDS extracts of both fungal forms for immunoblot. Immunofluorescence analysis revealed that this MAb reacted not only with mycelia and yeast cells, but also with conidia, indicating that this protein was shared by the three fungal propagules. By immunoelectron microscopy, this protein was detected in the cell walls and in the cytoplasm. Both the 32-kDa purified protein and MAb inhibited the adherence of conidia to the three extracellular matrix proteins in a dose-dependent manner. These findings demonstrate the presence of two polypeptides capable of interacting with extracellular matrix proteins on the surface of P. brasiliensis propagules, indicating that there may be common receptors for laminin, fibronectin, and fibrinogen. These proteins would be crucial for initial conidial adherence and perhaps also in dissemination of paracoccidioidomycosis.

Production of melanin has been associated with virulence in diverse microorganisms. Melanization of fungi has been noted for many years in predominantly subcutaneous infections such as chromoblastomycosis and more recently most extensively studied in a yeast causing systemic infection, Cryptococcus neoformans. Pigmented fungi are increasingly important human pathogens and currently available antifungals are often sub-optimal for serious infections. This review focuses on recent publications on melanin in fungi with particular reference to the role of melanin in virulence, protection against antifungal drugs, and promoting survival in the environment.Inhibition of melanin production by C. neoformans can prolong survival of lethally infected mice. In contrast, melanin in C. neoformans and Histoplasma capsulatum yeast cells can bind amphotericin B and caspofungin, thereby reducing the fungicidal affects of these drugs. H. capsulatum and Paracoccidioides brasiliensis have only recently been shown to produce melanin in vitro and during infection. Additionally, melanin derived from melanized C. neoformans yeast and Aspergillus niger conidia can activate complement, which may modify immune responses to infection. Studies on C. neoformans laccase have revealed that the enzyme is located on the cell wall, which may allow for interactions with the host. Melanization reduces the susceptibility of C. neoformans to enzymatic degradation and toxicity from a heavy metal, which may afford protection to the fungus against similar insults in the environment.Melanin has been referred to as 'fungal armor' due to the ability of the polymer to protect microorganisms against a broad range of toxic insults. Recent publications continue to reveal important contributions of melanin to survival of fungi in the environment and during infection.

Melanin is made by several important pathogenic fungi and has been implicated in the pathogenesis of a number of fungal infections. This study investigated whether the thermally dimorphic fungal pathogenHistoplasma capsulatumvar. capsulatumproduced melanin or melanin-like compounds in vitro and during infection. Growth ofH. capsulatummycelia in chemically defined minimal medium produced pigmented conidia. Growth ofH. capsulatumyeast in chemically defined minimal medium withl-3,4-dihydroxyphenylalanine (DOPA) or (-)-epinephrine produced pigmented cells. Treatment of the pigmented cells with proteolytic enzymes, denaturant, and hot concentrated acid yielded dark particles that were similar in size and shape to their respective propagules. Melanin-binding monoclonal antibodies (MAb) labeled pigmented conidia, yeast, and the isolated particles as determined by immunofluorescence microscopy. Electron spin resonance spectroscopy revealed that pigmented yeast cells and particles derived from pigmented cells were stable free radicals consistent with their identification as melanins. Tissues from mice infected withH. capsulatumand from biopsy specimens from a patient with histoplasmosis contained fungal cells that were labeled by melanin-binding MAb. Digestion of infected mouse tissues yielded dark particles that reacted with the melanin-binding MAb and were similar in appearance toH. capsulatumyeast cells. Additionally, sera from infected mice contained antibodies that bound melanin particles. Phenoloxidase activity capable of synthesizing melanin from L-DOPA was detected in cytoplasmic yeast cell extracts. These findings indicate thatH. capsulatumconidia and yeast can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role to play in the pathogenesis of histoplasmosis.

Melanins are implicated in the pathogenesis of several human diseases, including some microbial infections. In this study, we analyzed whether the conidia and the yeasts of the thermally dimorphic fungal pathogenParacoccidioides brasiliensisproduce melanin or melanin-like compounds in vitro and during infection. Growth ofP. brasiliensismycelia on water agar alone produced pigmented conidia, and growth of yeasts in minimal medium withl-3,4-dihydroxyphenylalanine (l-DOPA) produced pigmented cells. Digestion of the pigmented conidia and yeasts with proteolytic enzymes, denaturant, and hot concentrated acid yielded dark particles that were the same size and shape as their propagules. Immunofluorescence analysis demonstrated reactivity of a melanin-binding monoclonal antibody (MAb) with the pigmented conidia, yeasts, and particles. Electron spin resonance spectroscopy identified the yeast-derived particles produced in vitro whenP. brasiliensiswas grown inl-DOPA medium as a melanin-like compound. Nonreducing polyacrylamide gel electrophoresis of cytoplasmic yeast extract revealed a protein that catalyzed melanin synthesis froml-DOPA. The melanin binding MAb reacted with yeast cells in tissue from mice infected withP. brasiliensis. Finally digestion of infected tissue liberated particles reactive to the melanin binding MAb that had the typical morphology ofP. brasiliensisyeasts. These data strongly suggest thatP. brasiliensispropagules, both conidia and yeast cells, can produce melanin or melanin-like compounds in vitro and in vivo. Based on what is known about the function of melanin in the virulence of other fungi, this pigment may play a role in the pathogenesis of paracoccidioidomycosis.

Based on the difficulties experienced in the treatment of chromoblastomycosis, 12 primary human isolates of F. pedrosoi, were tested for their in vitro susceptibility to various antimycotics. We adapted the recommendations of the NCCLS for yeasts and followed the indications for mold testing from other authors in order to determine their MIC’s and the MLC’s. It was found that a significant proportion of the isolates were resistant to 3 of the 4 antimycotics tested, as revealed by high MIC values, as follows: 33% were resistant to amphotericin B (AMB), 58.3% to 5 fluocytosine (5 FC) and 66.7% to fluconazole (FLU). Contrarywise, none of the isolates proved resistant to itraconazole (ITZ). Determination of the MLC’s revealed that a larger proportion of the isolates were not killed by AMB, 5 FC (91.7%), FLU (100%) or even, ITZ (41.7%). These data indicate that it would be desirable to determine the susceptibility of F. pedrosoi before initiating therapy, in order to choose the more effective antifungal and avoid clinical failureTestes de suscetibilidade in vitro de Fonsecaea pedrosoi a antifúngicos Baseados nas dificuldades experimentadas no sucesso do tratamento da cromoblastomicose, 12 isolamentos humanos primários do F. pedrosoi foram examinados para a sua suscetibilidade in vitro aos vários antifúngicos. Nos adaptamos às recomendações da NCCLS feitas para leveduras e, seguimos as indicações para fungos filamentosos testados dadas por outros autores para as determinações dos MIC’s e dos MCLS. Nossos resultados mostraram que uma proporção significativa dos isolados testados foi resistente a três ou quatro dos antifúngicos experimentados, como revelaram os altos valores do MIC; assim, 33% dos isolados foram resistentes à anfotericina-B (AMB) 58,3% à fluorocitosina (5FC) e 66,7% ao fluconazole (FLU); pelo contrário, nenhum dos isolados examinados mostrou-se resistente ao itraconazole (ITZ). As determinações dos MLC revelaram que grande proporção dos isolados não foram mortos nem pela AMB (91,7%) 5FC (91,7%) FLU (100%) ou ainda, pelo ITZ (41,7%). Estes resultados indicam que seria muito desejável determinar a suscetibilidade do F. pedrosoi antes de começar o tratamento, para se poder escolher o antifúngico mais eficaz e evitar falha clínica

The diagnosis of endemic and invasive fungal disease remains challenging. Molecular techniques for identification of fungi now play a significant and growing role in clinical mycology and offer distinct advantages as they are faster, more sensitive and more specific. The aim of this mini-review is to provide an overview of the state of the art of molecular diagnosis of endemic and invasive fungal diseases, and to emphasize the challenges and current need for standardization of the different methods. The European Aspergillus PCR Initiative (EAPCRI) has made significant progress in developing a standard for Aspergillus polymerase chain reaction (PCR), but recognizes that the process will not be finished until clinical utility has been established in formal and extensive clinical trials. Similar efforts should be implemented for the diagnosis of the other mycoses in order to fully validate the current methods or reinforce the need to design new ones.This manuscript is part of the series of works presented at the 'V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi' (Oaxaca, Mexico, 2012). © 2013 Revista Iberoamericana de Micología.

Centre Hospitalier de Cayenne. Centre d Investigation Clinique Epid?miologie Clinique Antilles Guyane. Cayenne, French Guiana, France. / Universite? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana. Centre Hospitalier de Cayenne. Centre d Investigation Clinique Epid?miologie Clinique Antilles Guyane. Cayenne, French Guiana, France. / Universite? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana. Academisch Ziekenhuis Paramaribo Hospital. Paramaribo, Suriname. Laborat?rio Central de Sa?de P?blica do Amap?. Macap?, AP, Brazil. National AIDS Program. Georgetown, Guyana. Laborat?rio Central de Sa?de P?blica do Amap?. Macap?, AP, Brazil. Laborat?rio Central de Sa?de P?blica do Amap?. Macap?, AP, Brazil. Academisch Ziekenhuis Paramaribo Hospital. Paramaribo, Suriname. Public Health Central Laboratory of Suriname. Paramaribo, Suriname. Diakonessenhuis Hospital. Paramaribo, Suriname. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Hospital de Clinicas Dr. Alberto Lima. Macap?, AP, Brazil. Hospital de Clinicas Dr. Alberto Lima. Macap?, AP, Brazil. Universidade Federal do Cear? - Faculdade de Medicina - Departamento de Sa?de Comunitaria. Fortaleza, CE, Brazil. Corporaci?n para Investigaciones Biol?gicas. Medell?n, Colombia. Corporaci?n para Investigaciones Biol?gicas. Medell?n, Colombia Corporaci?n para Investigaciones Biol?gicas. Medell?n, Colombia INEI-ANLIS "Dr. Carlos G. Malbr?n". Buenos Aires, Argentina Universit? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana Universit? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana Centre Hospitalier de l'Ouest Guyanais. Saint Laurent du Maroni, French Guiana, France Centre Hospitalier de l'Ouest Guyanais. Saint Laurent du Maroni, French Guiana, France Centre Hospitalier de l'Ouest Guyanais. Saint Laurent du Maroni, French Guiana, France Centers for Disease Control and Prevention. Mycotic Diseases Branch. Atlanta, Georgia, United States of America Centers for Disease Control and Prevention. Mycotic Diseases Branch. Atlanta, Georgia, United States of America Centers for Disease Control and Prevention. Mycotic Diseases Branch. Atlanta, Georgia, United States of America Centers for Disease Control and Prevention. Mycotic Diseases Branch. Atlanta, Georgia, United States of America Institut Pasteur. National Reference Center for Mycoses and Antifungals. Molecular Mycology Unit. Paris, France Centre Hospitalier de Cayenne. Centre d Investigation Clinique Epid?miologie Clinique Antilles Guyane. Cayenne, French Guiana, France. / Universite? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana Universit? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana Academisch Ziekenhuis Paramaribo Hospital. Paramaribo, Suriname

Paracoccidioidomycosis (PCM) is a systemic, endemic fungal disorder restricted to Latin America (Mexico to Argentina); Brazil accounts for the largest number of cases. Imported cases diagnosed in North America, Europe and Asia represent patients who had previously lived in recognized endemic areas. Paracoccidioides brasiliensis, the etiologic agent, is a thermally dimorphic fungus that in patients and cultures at 37 C adopts a yeast form while at lower temperatures it behaves as a mold that bears the infectious conidia. PCM has a peculiar gender distribution with preference for adult males at a ratio of ?11 to 1. PCM afflicts predominantly adult males engaged in agriculture. It is mostly a chronic disease with acute/subacute cases accounting for less than 15 % of all reports. Specific diagnosis is established late and although available therapy is usually successful in controlling the fungal infection, patients who survive usually develop residual fibrotic lesions that heavily impair their quality of life. © 2012 Springer Science+Business Media New York.

Histoplasmosis is a frequent health problem in Latin American countries, but the fact that it is not a reportable disease prevents reliable estimates of its real incidence and impact on public health. Epidemiologic and clinical data remain patchy in general, and in some countries the information available is very limited. Histoplasmosis has a significant public health impact in susceptible populations such as immunosuppressed individuals, in whom the disease is associated with poor outcomes. Limited availability of diagnostic tools in many regions of Latin America is an additional problem, as many patients are already severely ill by the time of the diagnosis. Efforts are therefore necessary to ensure early diagnosis and appropriate treatment, limit the severity of the disease manifestations, and reduce morbidity and mortality. This paper reviews important aspects of the epidemiology of histoplasmosis, the most clinically significant endemic mycosis in Latin America. © Springer Science+Business Media, LLC 2011.

We aimed at determining involvement of extracellular matrix proteins (ECMp) and an ECM-binding adhesin (32-kDa protein) from Paracoccidioides brasiliensis, in the course of experimental paracoccidioidomycosis. BALB/c mice were infected with P. brasiliensis conidia previously incubated with soluble laminin, fibronectin and fibrinogen or a mAb against the fungal adhesin. Inflammatory response, chitin levels and cytokine production at different postinfection periods were determined. Chitin was significantly decreased in lungs of mice infected with ECMp-treated conidia when compared with controls at week 8, especially with laminin and fibrinogen. Contrariwise, when animals were infected with mAb-treated conidia no differences in chitin content were found. The observed inflammatory reaction in lungs was equivalent in all cases. IFN-g increased significantly in lungs from mice infected with soluble ECMp – (at day 4 and week 12) or mAb-treated conidia (at week 12) when compared with animals infected with untreated conidia. Significant increased levels of tumour necrosis factor-a were observed at 8 weeks in animals infected with ECMp-treated conidia while no differences were observed during the remaining periods. These findings point toward an inhibitory effect of ECMp on P. brasiliensis conidia infectivity and suggest that these proteins may interfere with conidia initial adhesion to host tissues probably modulating the immune response in paracoccidioidomycosis. COL0013709 COL0013746

The adhesion of microorganism to host cells or extracellular matrix (ECM) proteins is the first step in the establishment of an infectious process. Interaction between Paracoccidioides brasiliensis yeast cells and ECM proteins has been previously noted. In vivo, in the chronic phase of experimental paracoccidioidomycosis (PCM), laminin and fibronectin have been detected on the surface of yeast cells located inside granulomatous lesions. The aim of the present study was to examine the ability of P. brasiliensis yeast cells to interact with extracellular matrix proteins (laminin, fibrinogen and fibronectin) and to establish which molecules were involved in this interaction. Immunofluorescence microscopy and flow cytometry demonstrated that all three ECM proteins tested were able to bind to the surface of P. brasiliensis yeast cells. Treatment with trypsin, chymotrypsin, chitinase, proteinase K or different sugars resulted in no change in laminin binding. In addition, ligand affinity assays were performed using different yeast extracts (total homogenates, b-mercaptoethanol, SDS extracts). These assays demonstrated the presence of 19 and 32-kDa proteins in the cell wall with the ability to bind to laminin, fibrinogen and fibronectin. This interaction could be important in mediating attachment of the fungus to host tissues and may consequently play a role in the pathogenesis of PCM. COL0013709 COL0013746

Melanins are implicated in the pathogenesis of several important human diseases. This study confirmed the presence of melanin particles in Candida albicans in vitro and during infection. Dark particles were isolated from the digestion of C. albicans cultures and from infected tissue, as established by electron microscopy and immunofluorescence techniques.

Melanin has been implicated in the pathogenesis of several important human fungal pathogens. Existing data suggest that the conidia of the dimorphic fungal pathogen Sporothrix schenckii produce melanin or melanin-like compounds; in this study we aimed to confirm this suggestion and to demonstrate in vitro and in vivo production of melanin by yeast cells. S. schenckii grown on Mycosel agar produced visibly pigmented conidia, although yeast cells grown in brain heart infusion and minimal medium broth appeared to be nonpigmented macroscopically. However, treatment of both conidia and yeast cells with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles similar in shape and size to the corresponding propagules, which were stable free radicals consistent with identification as melanins. Melanin particles extracted from S. schenckii yeast cells were used to produce a panel of murine monoclonal antibodies (MAbs) which labeled pigmented conidia, yeast cells, and the isolated particles. Tissue from hamster testicles infected with S. schenckii contained fungal cells that were labeled by melanin-binding MAbs, and digestion of infected hamster tissue yielded dark particles that were also reactive. Additionally, sera from humans with sporotrichosis contained antibodies that bound melanin particles. These findings indicate that S. schenckii conidia and yeast cells can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role in the pathogenesis of sporotrichosis.

Bordetella bronchiseptica is an important veterinary pathogen but a rare cause of opportunistic respiratory tract infection in humans. We describe a case of pleural effusion caused by B. bronchiseptica in a patient with AIDS who was coinfected with Mycobacterium tuberculosis. To the best of our knowledge this is the first case in the medical literature in which the microorganism has been isolated from pleural fluid.

Nonculture based methods for the detection of infections caused by fungal pathogens are becoming more important tools in the management of infected patients. Detection of fungal antigens and DNA appear to be the most promising in this respect for both opportunistic and endemic mycoses. In this article we present an overview of the most recent developments in nonculture based methods and examine their value in clinical practice.

Paracoccidioidomycosis (PCM) is a primary pulmonary infection that often disseminates to other organs and systems. Involvement of the central nervous system (CNS) is rare and due to the fact that both clinical alertness and establishment of the diagnosis are delayed, the disease progresses causing serious problems. We report here a case of neuroparacoccidioidomycosis (NPCM), observed in a 55 year-old male, who consulted due to neurological symptoms (left hemiparesis, paresthesias, right palpebral ptosis, headache, vomiting and tonic clonic seizures) of a month duration. Upon physical examination, an ulcerated granulomatous lesion was observed in the abdomen. To confirm the diagnosis a stereotactic biopsy was taken; additionally, mycological tests from the ulcerated lesion and a bronchoalveolar lavage were performed. In the latter specimens, P. brasiliensis yeast cells were visualized and later on, the brain biopsy revealed the presence of the fungus. Treatment with itraconazole (ITZ) was initiated but clinical improvement was unremarkable; due to the fact that the patient was taking sodium valproate for seizure control, drug interactions were suspected and confirmed by absence of ITZ plasma levels. The latter medication was changed to clonazepam and after several weeks, clinical improvement began to be noticed and was accompanied by diminishing P. brasiliensis antigen and antibody titers. In the PCM endemic areas, CNS involvement should be considered more often and the efficacy of itraconazole therapy should also be taken into consideration. RESUMO: A paracoccidioidomicose (PCM) é infecção pulmonar primária que algumas vezes pode se disseminar a outros órgãos e sistemas. O envolvimento do sistema nervoso central (SNC) é raro e devido ao fato que a alerta clínica e o estabelecimento do diagnóstico são tardios, a doença progride e o paciente piora. Aquí apresentamos caso de neuroparacoccidioidomicose (NPCM) observada em homem de 55 anos de idade que referia sintomas neurológicos (hemiparalisia esquerda, parestesias, ptose pálpebral direita, dor de cabeça, vômito e convulsões) de um mes de duração. Ao exame físico, foi achada lesão ulcerada e granulomatosa no abdômen. Como o diagnóstico era duvidoso, foi indicada biopsia estereotáxica; além disso provas micológicas a partir da lesão ulcerada e um lavado broncoalveolar foram realizados. Nas últimas amostras P. brasiliensis foi observado e depois a biopsia do cérebro revelou a presença do fungo. O tratamento com itraconazol foi iniciado mas a melhoria clínica não foi detectável; devido ao fato que o paciente estava tomando valproato de sódio para o controle das convulsôes, foi suspeita interação entre os dois medicamentos, que foi confirmada pela ausência do nível plasmático do antimicótico. Este último medicamento foi trocado por clonazepam e depois de algumas semanas a melhoria clínica foi percebida e acompanhada pela diminuição dos títulos de antígenos e anticorpos do P. brasiliensis. Em áreas endêmicas, o envolvimento do SNC deve ser considerado em doentes com PCM e a eficácia do itraconazole deve ser considerada. COL0013709

Se indujo fibrosis pulmonar tras la inoculación de conidios de Paracoccidioides brasiliensis por vía intranasal en ratones BALB / c. La fibrosis se asoció con la formación de granulomas, aumento de la hidroxiprolina pulmonar y aumentos sostenidos del factor de necrosis tumoral tisular alfa y del factor de crecimiento transformante beta. Este estudio sugiere un papel de estas citocinas en la generación de fibrosis pulmonar asociada con enfermedades infecciosas granulomatosas crónicas. Pulmonary fibrosis was induced following inoculation of Paracoccidioides brasiliensis conidia intranasally in BALB/c mice. Fibrosis was associated with formation of granulomas, increase in lung hydroxyproline, and sustained increases in tissue tumor necrosis factor-alpha and transforming growth factor-beta. This study suggests a role for these cytokines in generation of pulmonary fibrosis associated with chronic granulomatous infectious diseases.

ResumenStreptococcus agalactiae es un coco Gram positivo que se encuentra frecuentemente asociado a infecciones en neonatos, mujeres embarazadas y adultos inmunocomprometidos.ObjetivoComparar la sensibilidad de los métodos para la recuperación y la determinación de la prevalencia de S. agalactiae en un grupo de mujeres gestantes de Medellín.Materiales y métodosSe llevó a cabo un estudio descriptivo de corte. La población estudiada fueron 362 mujeres gestantes que consultaron en el periodo comprendido entre febrero y octubre de 2008, a las que se les tomaron muestras con hisopo del introito vaginal y de la región anal. Las muestras secultivaron simultáneamente en agar Nueva Granada y caldo Todd Hewitt con suplemento de antibióticos, a partir del cual se hizo un subcultivo en agar sangre de carnero al 5%.ResultadosAl comparar el método de recuperación en agar Nueva Granada con el método de referencia en caldo Todd Hewitt, la sensibilidad del primero fue de 44% y el valor diagnóstico positivo de 58%; presentó una alta especificidad (98%) y un valor diagnóstico negativo de 99%. Se identificó S. agalactiae en 21 (5,8%) gestantes.ConclusiónEl cultivo en caldo Todd Hewitt es un método sensible para la recuperación de S. agalactiae. Por consiguiente, se recomienda continuar con esta metodología para la tamización de mujeres gestantes en nuestro medio. La prevalencia de 5,8% encontrada en este estudio concuerda con los reportes de la literatura mundial y, teniendo en cuenta que la tasa de transmisión vertical es, aproximadamente, de 50% (1), se demuestra la necesidad de implementar medidas de vigilancia epidemiológica en nuestro medio.Streptococcus agalactiae, is a Gram positive coccus that is frequently associated to infections in neonates, pregnant women, and immunocompromised adults.ObjectiveCompare method sensitivity for recovery from S. agalactiae and to determine its prevalence in a group of pregnant women of the city of Medellín.Materials and methodsCross-sectional descriptive study. The population was pregnant women of Medellín who consulted from February to October, 2008; 362 pregnant women were included; the samples were taken from vagina introitus and anal area. The samples were simultaneously cultured in New Granada Agar and Todd Hewitt Broth supplemented with antibiotics, which was the base for the performance of a subculture in Ram Blood Agar at 5%.ResultsWhen comparing the New Granada Agar method of recovery with the Todd Hewitt Broth gold test, the sensitivity of the first was 44% and the positive predictive value was 58%; it presented 98% specificity and a negative predictive value of 99%. S. agalactiae was found in 21 (5.8%) pregnant women.ConclusionsTodd Hewitt Broth is a sensitive method for the recovery from S. agalactiae; therefore, continuing with this methodology for the screening of pregnant women in our environment is recommended. The 5,8% prevalence found in this study is consistent with the reports in world-wide literature. Considering that the rate of vertical transmission is approximately 50%, the need to implement epidemiological surveillance measures in our environment is evident.

ResumenLa baja especificidad de los signos y síntomas presentes en el paciente con infección por el virus de inmunodeficiencia humana y con HDP concomitante dificulta grandemente su diagnóstico. La elección de la terapia antimicótica de inducción se basa en la valoración clínica de la gravedad del paciente, que lleva a la decisión del tratamiento inicial que afecta directamente a la mortalidad. Es muy importante, por consiguiente, identificar variables clínicas y de laboratorio que ayuden a evaluar el grado de afectación en el paciente con HDP y sida para, de esta manera, elegir rápida y adecuadamente la terapia de inducción. Se efectuó una búsqueda bibliográfica en PubMed y LILACS utilizando como palabras clave: histoplasmosis, prognosis, pronóstico y prognostic. Se seleccionaron artículos entre 1995 y 2011 con énfasis en estudios analíticos. Se identificaron variables clínicas y de laboratorio que predijeran de forma independiente el riesgo de mortalidad en pacientes con histoplasmosis y sida, tales como: disnea, falla renal aguda, insuficiencia respiratoria. En el laboratorio, se identificaron: concentración de hemoglobina < 8g/dL, recuento de plaquetas < 100.000/mm3, aspartato aminotransferasa 2,5 veces > la concentración normal, creatinina > 2,1mg/dL, albúmina < 3,5g/dL, lactato deshidrogenasa aumentada al doble de lo normal. Como factor protector al desarrollo de complicaciones, se identificó el uso previo de terapia antirretroviral. El reconocimiento de estas variables pudiera ser de gran utilidad para definir qué pacientes requerirían estrategias de tratamiento inicial y cuidado más agresivas.AbstractCurrently, clinical suspicion of histoplasmosis in AIDS patients is based on the evaluation of signs and symptoms presented by the patient, and on the use of nonspecific laboratory tests. The low specificity of the signs and symptoms seriously hinders their diagnosis. The choice of the initial antimycotic therapy is based on the clinical evaluation of the patients condition and this decision will directly affect mortality. It is therefore important to identify clinical and laboratory variables that could help to evaluate the degree of patient's involvement and in this way make a prompt and adequate choice of the induction therapy. We conducted a litera-ture search via PUBMED and LILACS using the key words histoplasmosis, prognosis, pronóstico and prognostic. We selected articles published between 1995 and 2011, making emphasis on analytical studies. We identified clinical and laboratory variables that independently predict the risk of mortality in AIDS patients with histoplasmosis including dyspnea, acute renal failure and respiratory insuficiency. As far as laboratory values, we identified the following variables: hemoglobin concentration less than 8g/dl, plaque count less than 100.000per mm3, aspar-tate aminotrasferase (AST) 2.5 times the normal concentration, creatinine above 2.1mg/dl, albumin below 3.5g/dl, lactate dehydrogenase (LDH) elevated to more than twice the normal value. As a protective factor at the onset of complications, we identified the previous use of antirretroviral therapy. The identification of these variables could be of much use for defining which patients would need more aggressive initial treatment and special care.