Endemic Mycoses Research Articles

Applying nanopore sequencing technology in Paracoccidioides sp.: a high-quality DNA isolation method for next-generation genomic studies.

Paracoccidioidomycosis is a severe systemic endemic mycosis caused by Paracoccidioides spp. which mainly affects individuals in Latin America. Progress in Paracoccidioides genomics has been slow, as evidenced by the incomplete reference databases available. Next-generation sequencing is a valuable tool for epidemiological surveillance and genomic characterization. With the ability to sequence long reads without the need for prior amplification, Oxford Nanopore Technology (ONT) offers several advantages, but high-quality and high-quantity DNA samples are required to achieve satisfactory results. Due to the low concentration of Paracoccidioides DNA in clinical samples and inefficient culture isolation methods, DNA extraction can be a significant barrier to genomic studies of this genus. This study proposes a method to obtain a high-coverage de novo genome assembly for Paracoccidioides using an improved DNA extraction method suitable for sequencing with ONT. The assembly obtained was comparable in size to those constructed from available data from Illumina technology. To our knowledge, this is the first genome assembly of Paracoccidioides sp. of such a large size constructed using ONT.

Clinical Characteristics and Mortality Risks Among Patients With Culture-Proven Coccidioidomycosis Who Are Critically Ill: A Multicenter Study in an Endemic Region.

Coccidioidomycosis is an endemic mycosis in the southwestern United States. While most infections are mild, severe cases can be devastating. We aimed to describe the clinical characteristics and mortality risks of patients in the intensive care unit (ICU) with culture-proven coccidioidomycosis. We performed a retrospective chart review of patients in the ICU with positive Coccidioides spp culture in a large health care system in Arizona between 1 October 2017 and 1 July 2022. All data were entered into REDCap. An overall 145 patients were identified and included. The median age was 51 years, with the majority male (69%) and non-Hispanic White (39%). Most patients (n = 104, 72%) had pulmonary coccidioidomycosis, and 41 had extrapulmonary disease (17 meningitis, 13 fungemia, 10 musculoskeletal disease, and 4 pericardial or aortic involvement). Seventy patients (48%) died during hospitalization, and most (91%) received antifungal therapy during hospitalization. In the multivariate logistic regression model, age ≥60 years (odds ratio [OR], 7.0; 95% CI, 2.6-18.8), cirrhosis (OR, 13.1; 95% CI, 1.6-108.8), and mechanical ventilation or vasopressor support (OR, 15.4; 95% CI, 3.9-59.6) were independently associated with increased all-cause mortality, but pre-ICU antifungal use had a statistically insignificant mortality risk association (OR, 0.5; 95% CI, .2-1.2). In our study of patients in the ICU with coccidioidomycosis and multiple comorbidities, the mortality rate was high. Older age, cirrhosis, and mechanical ventilation or vasopressor support were significantly associated with high mortality. Future studies are recommended to evaluate those risk factors and the efficacy of rapid diagnosis and early therapy in patients at high risk.

Endemic pediatric fungal infections in India: clues to diagnosis.

This review is intended to familiarize readers with an emerging group of fungal infections that mostly manifest in immunocompetent individuals. This group was initially considered endemic to the tropics, but increasing worldwide prevalence has been reported. The organisms have been divided into dominant non-invasive forms and dominant invasive forms for ease of understanding. The non-invasive organisms include the group Entomophthoromycota, under which two genera Basidiobolus and Conidiobolus, have been identified as human pathogens. They present with plaques in the extremities and rhinofacial region, respectively. The invasive organisms are dematiaceous fungi (phaeohypomycosis), which includes Cladophialophora and Exophiala among others. They cause invasion of deep tissues, with the central nervous system being the most common target. The mycology, epidemiology, diagnosis, and treatment options have been summarized in brief. The clinical presentation, imaging manifestations, differentiation from other common infections and malignancies that show similar features have been detailed.

Molecular Diagnostics for Invasive Fungal Diseases: Current and Future Approaches.

Invasive fungal diseases (IFDs) comprise a growing healthcare burden, especially given the expanding population of immunocompromised hosts. Early diagnosis of IFDs is required to optimise therapy with antifungals, especially in the setting of rising rates of antifungal resistance. Molecular techniques including nucleic acid amplification tests and whole genome sequencing have potential to offer utility in overcoming limitations with traditional phenotypic testing. However, standardisation of methodology and interpretations of these assays is an ongoing undertaking. The utility of targeted Aspergillus detection has been well-defined, with progress in investigations into the role of targeted assays for Candida, Pneumocystis, Cryptococcus, the Mucorales and endemic mycoses. Likewise, whilst broad-range polymerase chain reaction assays have been in use for some time, pathology stewardship and optimising diagnostic yield is a continuing exercise. As costs decrease, there is also now increased access and experience with whole genome sequencing, including metagenomic sequencing, which offers unparalleled resolution especially in the investigations of potential outbreaks. However, their role in routine diagnostic use remains uncommon and standardisation of techniques and workflow are required for wider implementation.

Antifungal efficacy and immunomodulatory effect of PLGA nanoparticle-encapsulated itraconazole in histoplasmosis in vivo model

IntroductionHistoplasma capsulatum is the etiological agent of histoplasmosis, the most common endemic pulmonary mycosis. Itraconazole (ITZ) is the choice for mild disease and a step-down therapy in severe and disseminated clinical presentations. Drug encapsulation into nanoparticles (NPs) is an alternative to improve drug solubility and bioavailability, reducing undesirable interactions and drug degradation and reaching the specific therapeutic target with lower doses. Objectiveevaluate the antifungal and immunomodulatory effect of ITZ encapsulated into poly(lactic-co-glycolic acid) (PLGA) NPs, administrated orally and intraperitoneally in an in vivo histoplasmosis model. ResultsAfter intranasal infection and treatment of animals with encapsulated ITZ by intraperitoneal and oral route, fungal burden control, biodistribution, immune response, and histopathology were evaluated. The results showed that the intraperitoneal administered and encapsulated ITZ has an effective antifungal effect, significantly reducing the Colony-Forming-Units (CFU) after the first doses and controlling the infection dissemination, with a higher concentration in the liver, spleen, and lung compared to the oral treatment. In addition, it produced a substantial immunomodulatory effect on pro- and anti-inflammatory cytokines and immune cell infiltrates confirmed by histopathology. ConclusionsOverall, results suggest a synergistic effect of the encapsulated drug and the immunomodulatory effect contributing to infection control, preventing their dissemination.

Suspected Case of Histoplasmosis-Related Immune Reconstitution Inflammatory Syndrome Manifesting as Unilateral Pleural Effusion

Background: Histoplasmosis is a prevalent endemic mycosis that frequently causes opportunistic infections among individuals living with HIV (human immunodeficiency virus), and acquired immunodeficiency syndrome (AIDS). The initiation of antiretroviral therapy (ART) can result in a rare histoplasma-associated immune reconstitution inflammatory syndrome (IRIS) that may be difficult to distinguish between active progressive disease and inflammatory reaction to the medication. Case report: A 35-year-old male with newly diagnosed HIV and cervical biopsy-confirmed histoplasmosis was admitted from the emergency department with disseminated histoplasmosis for HIV antiretroviral treatment and antifungal treatment. Discharged after a 2-week inpatient treatment the patient returned 1 week later with a large left pleural effusion. Two liters of serosanguinous fluid were removed and all fluid cultures and cytology were negative. An extensive work-up remained negative, and given the timeline of presentation in relation to the initiation of ART, it was felt that this isolated left-sided pleural effusion was a manifestation of IRIS. Eventually, corticosteroids were given for IRIS and the patient improved and was discharged on long-term treatment. Conclusions: Immunocompromised subjects are at serious risk for a virulent, aggressive, rapidly advancing histoplasma infection and should be counselled accordingly. Any clinical signs or symptoms of organ system deterioration or compromise should be reported to the provider and a workup for histoplasmosis considered. In patients treated with antiretrovirals, IRIS is particularly confounding since it is difficult to differentiate from active disease. Using corticosteroids in already immunocompromised patients with an established fungal infection requires caution. Compliance with treatment is one of the most important components of care, especially considering the months of protocol.

Phenotypic characterization of cryptic species in the fungal pathogen Histoplasma.

Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease, Histoplasma, is a dimorphic fungus commonly found in the soil where it grows as mycelia. Humans can become infected by Histoplasma through inhalation of its spores (conidia) or mycelial particles. The fungi transition into the yeast phase in the lungs at 37°C. Once in the lungs, yeast cells reside and proliferate inside alveolar macrophages. Genomic work has revealed that Histoplasma is composed of at least five cryptic phylogenetic species that differ genetically. Three of those lineages have received new names. Here, we evaluated multiple phenotypic characteristics (colony morphology, secreted proteolytic activity, yeast size, and growth rate) of strains from five of the phylogenetic species of Histoplasma to identify phenotypic traits that differentiate between these species: Histoplasma capsulatum sensu stricto, Histoplasma ohiense, Histoplasma mississippiense, Histoplasma suramericanum, and an African lineage. We report diagnostic traits for three species. The other two species can be identified by a combination of traits. Our results suggest that (i) there are significant phenotypic differences among the cryptic species of Histoplasma and (ii) those differences can be used to positively distinguish those species in a clinical setting and for further study of the evolution of this fungal pathogen.IMPORTANCEIdentifying species boundaries is a critical component of evolutionary biology. Genome sequencing and the use of molecular markers have advanced our understanding of the evolutionary history of fungal pathogens, including Histoplasma, and have allowed for the identification of new species. This is especially important in organisms where morphological characteristics have not been detected. In this study, we revised the taxonomic status of the four named species of the genus Histoplasma, H. capsulatum sensu stricto (ss), H. ohiense, H. mississippiense, and H. suramericanum, and propose the use of species-specific phenotypic traits to aid their identification when genome sequencing is not available. These results have implications not only for evolutionary study of Histoplasma but also for clinicians, as the Histoplasma species could determine the outcome of disease and treatment needed.

Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease.

SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, and their utility and efficacy in antifungal treatment are limited by one or more of innate or acquired resistance in some fungi, poor penetration into "sequestered" sites, and agent-specific side effect which require frequent patient reassessment and monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, and fungicidal mechanism(s) are urgently needed. Here, we provide a comprehensive review of novel antifungal agents, with both improved known mechanisms of actions and new antifungal classes, currently in clinical development for treating invasive yeast, mold (filamentous fungi), Pneumocystis jirovecii infections, and dimorphic fungi (endemic mycoses). We further focus on inhaled antifungals and the role of immunotherapy in tackling fungal infections, and the specific PK/pharmacodynamic profiles, tissue distributions as well as drug-drug interactions of novel antifungals. Finally, we review antifungal resistance mechanisms, the role of use of antifungal pesticides in agriculture as drivers of drug resistance, and detail detection methods for antifungal resistance.

Tracing histoplasmosis genomic epidemiology and species occurrence across the USA

ABSTRACT Histoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.

Histoplasmosis Beyond Human Immunodeficiency Virus (HIV): Clinical Characteristics and Outcomes in a Non-HIV Population.

Histoplasmosis is an endemic and invasive mycosis caused by Histoplasma capsulatum. We conducted a retrospective study comparing immunosuppressed patients without human immunodeficiency virus (HIV) with a historical cohort of people with HIV and histoplasmosis. We included 199 patients with proven or probable histoplasmosis, of which 25.1% were people without HIV. Diabetes mellitus, chronic kidney disease, hematologic neoplasms, rheumatologic diseases, and transplantations were more frequent among people without HIV (P < .01). Forty-four percent of immunocompromised patients without HIV died within the first 6-week period following their diagnosis. A high suspicion index for histoplasmosis should be kept in immunosuppressed patients.

MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial.

Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. NCT03572049.

Clinical-epidemiological characteristics of paracoccidioidomycosis and presence of Paracoccidioides spp. in the natural environment in Rio Grande do Sul, southern Brazil: an 81-year literature survey

Paracoccidioidomycosis (PCM), caused by fungi of the genus Paracoccidioides, is the main endemic mycosis in Brazil, with serious social and public-health impacts. Although the state of Rio Grande do Sul in southern Brazil is an area of high endemicity, data on PCM in this state are very sparse. Here, an exhaustive literature search was conducted for PCM cases reported in Rio Grande do Sul, in addition to the environmental occurrence of Paracoccidioides spp. in the state. From 1942 to 2023, 52 studies were found, encompassing a total of 1576 PCM cases. The male : female ratio was 15 : 1, and the most affected age group was 41–60 years. Lesions were reported at 11 different anatomical sites, with a predominance of the lungs and upper aerodigestive tract mucosa. Data such as treatment and mortality were rarely reported. Cases were recorded in 30% of the municipalities in the state, predominantly in the northern region. Regarding the environmental presence of Paracoccidioides spp., anti-P. brasiliensis and anti-P. lutzii antibodies have been identified in several animal species in addition to isolation of the fungi from soil samples. Although a literature search is useful for a basic knowledge of PCM occurrence, the need for epidemiological surveillance of the disease in Rio Grande do Sul is urgent, considering its high endemicity and occurrence in all regions of the state.

22-Year-Old with Invasive Mass of the Right Femur

Blastomyces dermatitidis is an endemic mycosis in certain regions of the United States of America and can cause disseminated infection in immunocompetent individuals. We present a case of osseous blastomycosis in a previously healthy 22-year-old male from Missouri, who developed sudden onset right knee pain in June 2019. Magnetic Resonance Imaging (MRI) demonstrated an enhancing mass that was concerning for osseous malignancy. Antigen and antibody testing for dimorphic fungi was confounding. He underwent debridement and surgical specimen cultures grew B. dermatitidis. He was treated initially with liposomal amphotericin B and transitioned to oral itraconazole to complete therapy. Blastomycosis of the bone can be mistaken for malignancy and should be included on a differential for these types of cases. Blastomycosis of the bone and joints can be successfully treated with surgical debridement and prolonged antifungal therapy.

872. Characterizing Plasma Microbial Cell-Free DNA Sequencing Detections of Public Health Important Pathogens

Abstract Background Timely pathogen identification is critical for meaningful disease surveillance to facilitate effective public health responses. However, public health important pathogens are often diagnostically challenging (e.g., indeterminate serological results, multiple samples separated by long intervals, lengthy turnaround times) and at odds with public health needs. We describe detections of public health important pathogens by the Karius Test®, a validated plasma microbial cell-free DNA (mcfDNA) sequencing test, providing real-time pathogen detection. Methods We identified nationally notifiable infectious diseases (NNID)-associated and selected state reportable pathogens detected and quantified as DNA molecules/μl (MPM) in US patients’ plasma samples submitted to the Karius CLIA certified/CAP accredited laboratory for mcfDNA sequencing between 4/1/18–4/30/22. We evaluated and characterized these detections based on result and test requisition form data. We reviewed gender and immunocompromised status of a subset of patients linked deterministically to the Premier Healthcare Database (PHD), a US hospital-based, all-payer database. Results Plasma mcfDNA sequencing yielded 520 detections of 62 microbes associated with 27 NNIDs and 449 detections of an additional 12 microbes, including public health important parasites, amoebae, endemic mycoses, and selected bacteria, across 27 US states. MPM and patient age varied widely across microbes from 9–300+ million and 0–89 years, respectively (Table 1). For the 167 (17%) PHD-linked detections, 71% were associated with male and 72% with immunocompromised patients. Conclusion Plasma mcfDNA sequencing detected many different public health important pathogens across many states, especially among immunocompromised patients. These patients pose a heightened public health concern given their increased risk for more severe disease and potential for longer infectious periods and greater likelihood of atypical or nonspecific presentations, leading to greater risk of unrecognized disease spread. Plasma mcfDNA sequencing, an unbiased test, may contribute to rapidly identifying disease outbreaks and spread, and facilitate timely interventions to improve public health. Disclosures Constance Lau, MPH, Karius, Inc.: Stocks/Bonds David Berman, DO, Precision Health Solutions, St. Petersburg, Florida: Advisor/Consultant Frederick S. Nolte, PhD, Karius: Stocks/Bonds

Progressive disseminated histoplasmosis: The experience in one non-endemic medical center.

Histoplasmosis, the most common endemic mycosis in North America, presents in a myriad of ways, spanning the spectrum from self-limiting pneumonia to progressive disseminated histoplasmosis (PDH). Toward better describing contemporary histoplasmosis syndromes, risks, and outcomes, this single-center retrospective cohort study was performed (2009-2019). The population who developed PDH was similar to that with other forms of histoplasmosis (OFH) except for higher rates of preexisting immunocompromising conditions (91.3% vs. 40%, P<.001) and a trend toward receiving more chronic immunosuppression (65.2% vs. 33.3%, P=.054) compared to those with OFH. Diagnosis was most frequently achieved by urinary or serum antigen positivity. People with PDH more frequently tested positive compared to those with OFH, but negative tests did not rule out histoplasmosis. Median time to diagnosis was prolonged among people with both PDH and OFH (32 vs. 31 days, respectively). Following diagnosis, people with PDH received more liposomal amphotericin (78.3% vs. 20%, P<.001). Subsequent survival at 90 and 365 days and treatment response were similar in both groups. Patients with PDH were more often hospitalized (95.7% vs. 60%, P=.006); however, once admitted, there were no differences in hospital length of stay or intensive care unit admission rate. The challenges of diagnosing histoplasmosis based on clinical presentation alone highlight the need for heightened awareness of these entities especially given the recent reports on expanded endemicity and delays in diagnosis.

Facial Sporotrichosis by Sporothrix Brasiliensis in a Pediatric Patient: Case Report

Sporotrichosis is an endemic subcutaneous mycosis in Brazil, which zoonotic transmission through infected cats became responsible for the actual spread of the disease in the country. In this new epidemiological scenario, the species Sporothrix brasiliensis became relevant thanks to its greater virulence and adaptation to felines. We reported the case of facial sporotrichosis by S. brasiliensis in a 7-year-old child, successfully treated with a saturated potassium iodide solution, proving that this medication is safe and efficient for this age group.

Emergomycosis, an Emerging Thermally Dimorphic Fungal Infection: A Systematic Review.

Emergomycosis is an endemic mycosis caused by the Emergomyces species. Infections due to this agent have been reported globally. Hence, the present systematic review on Emergomyces infections was conducted to study the disease epidemiology, underlying diseases and risk factors, causative agents, and treatment and outcome. The MEDLINE, Scopus, Embase, and Web of Science databases were searched systematically with appropriate keywords from January 1990 to October 2022. A total of 77 cases of emergomycosis were included in the analysis. Emergomycosis was most commonly seen in patients with human immunodeficiency virus (HIV) infection (n = 61, 79.2%) and HIV-uninfected patients with or without other comorbidities (n = 16, 20.8%). The underlying disease and risk factors significantly associated with emergomycosis in the HIV-infected patients were CD4+ T-cell counts less than 100 cells/mm3 (n = 55, 90.2%), anaemia (n = 30, 49.2%), and thrombocytopenia (n = 17, 27.9%), whereas in the HIV-uninfected patients, treatment with immunosuppressive drugs (n = 10, 62.5%), renal disease (n = 8, 50%), transplant recipients (n = 6, 37.5%), and diabetes mellitus (n = 4, 25%) were the significant risk factors associated with emergomycosis. Emergomyces africanus (n = 55, 71.4%) is the most common causative agent, followed by E. pasteurianus (n = 9, 11.7%) and E. canadensis (n = 5, 6.5%). E. africanus was most often isolated from HIV-infected patients (n = 54, 98.2%), whereas E. pasteurianus was most common in HIV-uninfected patients (n = 5, 55.6%). The all-cause mortality rate of the total cohort is 42.9%. No significant variation in the mortality rate is observed between the HIV-infected patients (n = 28, 36.4%) and the HIV-uninfected patients (n = 5, 6.5%). In conclusion, with an increase in the immunosuppressed population across the globe in addition to HIV infection, the case burden of emergomycosis may increase in the future. Hence, clinicians and mycologists should be vigilant and clinically suspicious of emergomycosis, which helps in early diagnosis and initiation of antifungal treatment to prevent disease mortality.

Shoulder Coccidioidomycosis Masquerading as Synovial Chondromatosis

Coccidioidomycosis is an endemic fungal infection in arid areas of Southwestern US and Northern Mexico. It is difficult to diagnose and treat, may take years to make the correct diagnosis, may leave sequelae and could even be fatal.

Trends in the Epidemiological and Clinical Profile of Paracoccidioidomycosis in the Endemic Area of Rio de Janeiro, Brazil.

Paracoccidioidomycosis (PCM) is a neglected endemic mycosis in Latin America. Most cases occur in Brazil. It is classified as PCM infection and PCM disease and is subdivided into chronic (adult type) or acute (juvenile type) disease, with the latter being less frequent and more severe. In 2016, we reported an increase in the numbers of patients diagnosed with acute PCM after a highway's construction. We conducted a study at INI-Fiocruz, a reference center for infectious diseases, including endemic mycoses, in Rio de Janeiro, Brazil, aiming to deepen the analysis of this new clinical and epidemiological profile of PCM. The authors developed a retrospective study including 170 patients diagnosed with PCM between 2010 and 2019. There was an increase in the number of atypical and severe forms, starting in 2014. In subsequent years, we detected a higher incidence of adverse outcomes with patients requiring more hospitalizations and an increased mortality rate. We estimate that PCM has become more severe throughout the Rio de Janeiro state, affecting a greater number of young individuals and leading to a greater number of and longer hospitalizations. Surveillance measures and close monitoring of future notification data in the state, with emphasis on children, adolescents, and young adults are necessary for a better understanding of the perpetuation of this public health challenge.

Structure of glyceraldehyde-3-phosphate dehydrogenase from Paracoccidioides lutzii in complex with an aldonic sugar acid

The pathogen Paracoccidioides lutzii (Pb01) is found in South America countries Colombia, Ecuador, Venezuela and Brazil, especially in the central, west, and north regions of the latter. It belongs to the Ajellomycetaceae family, Onygenales order, and is typically thermodimorphic, presenting yeast cells when it grows in animal tissues, but mycelia when in the environment, where it produces the infectious propagule. This fungus is one of the etiologic agents of Paracoccidioidomycosis (PCM), the most important endemic fungal infection in Latin America. Investigations on its genome have contributed to a better understanding about its metabolism and revealed the complexity of several metabolic glycolytic pathways. Glyceraldehyde-3-Phosphate Dehydrogenase from Paracoccidioides lutzii (PlGAPDH) is considered a moonlighting protein and participates in several biological processes of this pathogen. The enzyme was expressed and purified, as seen in SDS-PAGE gel, crystallized and had its three dimensional structure (3D) determined in complex with NAD+, a sulphate ion and d-galactonic acid, therefore, a type of ‘GAA site’. It is the first GAPDH structure to show this chemical type in this site and how this protein can bind an acid derived from oxidation of a linear hexose.