Publications by authors named "Mario León Silva-Vergara"

63 Publications

Physical capacity, body composition and immune-inflammatory markers are associated with risk of cardiovascular disease in sedentary people living with HIV.

Minerva Cardiol Angiol 2021 Mar 11. Epub 2021 Mar 11.

Postgraduate Program in Physical Education, Federal University of Triângulo Mineiro, Uberaba, Brazil.

Background: People living with HIV (PLHIV) are experiencing a high level of non-HIV-related disease mainly related to cardiovascular system however the factors associated with this scenario are widely discussed and indefinite so far. The purpose was to investigate the association of physical capacities, body composition, and immuneinflammatory markers with the Framingham risk score (FRS) in PLHIV.

Methods: Volunteers were recruited and data on age, the time of HIV infection diagnosis and the time of HAART use were collected. The volunteers performed upper limb strength (ULS), lower limb strength (LLS) and cardiorespiratory fitness (VO2peak) tests, body composition evaluation, and blood collection to immune-inflammatory marker markers and the FRS was calculated. Partial age- and sex-adjusted correlation was used to verify associations between factors and multiple linear regression analysis was performed to identify an independent association of FRS and the variables.

Results: 113 PLHIV met the eligible criteria and were observed a negative correlation between CD4+ (r= - 0.615), time of HIV infection diagnosis (r= -0.237), time of HAART use (r= -0.239), ULS (r= -0.274), LLS (r= -0.213), and VO2peak (r= -0.207) with FRS. There was a positive correlation between fibrinogen and FRS (r= 0.363; p< 0.001). The TCD4+ count cells were significantly associated with FRS (p= 0.001).

Conclusions: Environmental and biological HIV-related factors are inversely associated with FRS while immuneinflammation markers have a positive association.
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http://dx.doi.org/10.23736/S2724-5683.21.05578-XDOI Listing
March 2021

Fatal Case of Fungemia by in a Pediatric Patient Diagnosed in a Teaching Hospital from Brazil.

J Fungi (Basel) 2020 Aug 25;6(3). Epub 2020 Aug 25.

Department of Microbiology, Immunology and Parasitology, Federal University of Triangulo Mineiro, Uberaba 38015-050, Brazil.

In recent decades, emerging fungal infections have changed the clinical mycology scenario as a consequence of the advances in medical diagnostics and therapeutic procedures, long hospitalization times, and the growing number of individuals with debilitating chronic diseases and impaired immune systems. This report presents a 19 months old Brazilian female patient who developed a severe fungal sepsis by an uncommon yeast. She was admitted at the intensive care unit with severe pneumonia, bronchopulmonary dysplasia, and weight-for-age z score of less than -2. She remained more than 30 days in the intensive care unit where she had a femoral venous catheter placement, enteral nutrition, broad-spectrum antibiotic therapy, and prophylaxis with fluconazole. Moreover, pericardiocentesis was performed due to cardiac tamponade. She had a previous history of prematurity, cardiac surgery due to patent ductus arteriosus, and a long period of hospital stay. Despite the antifungal prophylaxis, two yeast isolates were recovered from blood and then identified by classical mycological methods and internal transcribed spacer (ITS) sequencing as . Both isolates exhibited susceptibility to amphotericin B, ketoconazole, itraconazole, voriconazole, and fluconazole. Her clinical state worsened, presenting anasarca, epistaxis, and hemorrhagic suffusions in the mouth, sclera, oliguria, and bradycardia. Two days after the first positive culture, she presented a gradual reduction of the white blood cells count, with severe leukopenia and neutropenia. She died five days after.
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http://dx.doi.org/10.3390/jof6030147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558373PMC
August 2020

Daily Undulating Periodization Is More Effective Than Nonperiodized Training on Maximal Strength, Aerobic Capacity, and TCD4+ Cell Count in People Living With HIV.

J Strength Cond Res 2020 Jun 24. Epub 2020 Jun 24.

Exercise Science, Health and Human Performance Research Group, Department of Sport Sciences, Postgraduate Program in Physical Education, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.

Soares, VL, Soares, WF, Zanetti, HR, Neves, FF, Silva-Vergara, ML, and Mendes, EL. Daily undulating periodization is more effective than nonperiodized training on maximal strength, aerobic capacity, and TCD4+ cell count in people living with HIV. J Strength Cond Res XX(X): 000-000, 2020-The aim of this study was to evaluate the effects of daily undulating periodization (DUP) and nonperiodized training (NPT) programs on maximal muscle strength, body composition, aerobic capacity, muscle power, and immune markers in people living with HIV (PLWHIV). A total of 41 PLWHIV were randomly assigned to control (CON [n = 15]), DUP (n = 13), and NPT (n = 13) groups. The DUP and NPT groups performed combined training 3 times a week on nonconsecutive days during 12 weeks, whereas the CON group was asked to maintain their current level of activity. After the 12-week training program, DUP produced greater gains in muscle strength (except for bench press), V[Combining Dot Above]O2peak, and muscle power than NPT (p < 0.05). Compared to CON, the training groups showed significantly (p < 0.05) increased muscle strength (DUP = 31.0 ± 13.9 kg; NPT = 17.7 ± 9.2 kg; CON = -0.3 ± 1.5 kg), fat-free mass (DUP = 1.9 ± 1.5 kg; NPT = 1.4 ± 1.9 kg; CON = -0.1 ± 1.2 kg), and metabolic equivalent (DUP = 2.3 ± 1.3; NPT = 1.8 ± 1.9), and decreased body fat mass (DUP = -2.1 ± 1.6 kg; NPT = -1.4 ± 1.5 kg; CON = 0.1 ± 0.2) and functional aerobic impairment (DUP = -35.9 ± 17.0%; NPT = -25.8 ± 22.0%; CON = 0.8 ± 3.0%). There was an increase in TCD4 cells only in the DUP group (p < 0.05). The training effect generally provided a positive correlation between change in leg press strength (r = 0.393, p < 0.05), triceps pulley strength (r = 0.417, p < 0.05), lat pull-down strength (r = 0.459, p < 0.05), and muscle power (r = 0.324, p < 0.05) with changing CD4 + lymphocyte count. Daily undulating periodization protocol showed to be safe, applicable, and more efficient for increasing strength, aerobic capacity, and TCD4 cells compared to NPT in PLWHIV.
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http://dx.doi.org/10.1519/JSC.0000000000003675DOI Listing
June 2020

High genetic variability of clinical and environmental Cryptococcus gattii isolates from Brazil.

Med Mycol 2020 Nov;58(8):1126-1137

Infectious Diseases Unit, Internal Medicine Department, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.

Among Cryptococcus gattii genotypes, VGII has gained pivotal relevance in epidemiological, clinical and genetic contexts due to its association with several outbreaks in temperate regions and due to the high variability of this genotype. The aim of this study was to compare 25 isolates of C. gattii from the Southeast region of Brazil with previously described isolates from other regions of the country and around the world. Among the 25 isolates, 24 were VGII and one was VGI. All of them were newly identified. Three new allele types (AT) (AT47 for the URA5 locus, AT56 for the LAC1 locus, and AT96 for the IGS1 region) were also described. Compared with other Brazilian isolates, those from the Southeast region presented the greatest haplotype diversity. In general, the regions presented different sequence types (STs), and only nine STs were found in more than one location. GoeBURST analysis showed two large groups among the Brazilian isolates. The largest group consists of 59 STs predominantly from the North and Northeast regions; the other large group includes 57 STs from the Southeast and Midwest regions. In a global context the South American isolates presented the highest genetic diversity (STs = 145, haplotype diversity (Hd) = 0.999 and π = 0.00464), while the African populations showed the lowest genetic diversity (STs = 3, Hd = 0.667 and π = 0.00225). These results confirm that the Brazilian C. gattii VGII population is highly diverse and reinforce the hypothesis of dispersion of this genotype from South America.
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http://dx.doi.org/10.1093/mmy/myaa019DOI Listing
November 2020

Synergic effect of simvastatin in combination with amphotericin B against environmental strains of Cryptococcus neoformans from northeastern Brazil: a prospective experimental study.

Sao Paulo Med J 2020 Jan-Feb;138(1):40-46

PhD. Associate Professor, Department of Biomedicine, Universidade Federal do Triângulo Mineiro, Uberaba (MG), Brazil.

Background: Statins are used as cholesterol-lowering drugs and may also have direct antimicrobial effects.

Objective: To evaluate synergic interactions between simvastatin and both amphotericin B and fluconazole, against environmental strains of Cryptococcus neoformans isolated from captive birds' droppings.

Designand Setting: Experimental study conducted at Federal University of Piauí, Parnaíba, in collaboration with Federal University of Triângulo Mineiro, Uberaba, Brazil.

Methods: Statin susceptibility tests of Cryptococcus neoformans samples were performed as prescribed in standards. Interactions of simvastatin with amphotericin and fluconazole were evaluated using the checkerboard microdilution method. Presence of these interactions was quantitatively detected through determining the fractional inhibitory concentration index (FICI).

Results: Isolates of Cryptococcus neoformans were obtained from 30 of the 206 samples of dry bird excreta (14.5%) that were collected from pet shops and houses. Ten isolates were selected for susceptibility tests. All of them were susceptible to amphotericin and fluconazole. All presented minimum inhibitory concentration (MIC) > 128 µg/ml and, thus, were resistant in vitro to simvastatin. An in vitro synergic effect was shown through combined testing of amphotericin B and simvastatin, such that six isolates (60%) presented FICI < 0.500. Two isolates showed considerable reductions in MIC, from 1 µg/ml to 0.250 µg/ml. No synergic effect was observed through combining fluconazole and simvastatin.

Conclusion: These results demonstrate that simvastatin should be considered to be a therapeutic alternative, capable of potentiating the action of amphotericin B. However, further studies are necessary to clarify the real effect of simvastatin as an antifungal agent.
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http://dx.doi.org/10.1590/1516-3180.2019.0107.R2.16092019DOI Listing
July 2020

Histoplasmosis in HIV-Infected Patients: Epidemiological, Clinical and Necropsy Data from a Brazilian Teaching Hospital.

Mycopathologia 2020 Apr 20;185(2):339-346. Epub 2020 Feb 20.

Infectious Diseases Unit, Internal Medicine Department, Triângulo Mineiro Federal University, Mailbox 118, Uberaba, Minas Gerais, 38001-170, Brazil.

Histoplasmosis occurs in 5-10% of HIV-infected patients in endemic areas and evolves to severe and disseminated infection with mortality rates over 50% in some regions. This report presents epidemiological, clinical and outcome data from HIV-infected patients with histoplasmosis confirmed by culture and/or at necropsy who were admitted to a Brazilian teaching hospital. Data from 65 patients were obtained from their respective medical and necropsy records. From 2005 to 2018, 36 HIV-infected patients were diagnosed with histoplasmosis confirmed by culture. At admission, most of these patients presented disseminated fungal infection, whereas 15 (41.7%) were simultaneously diagnosed with both HIV infection and histoplasmosis. Fever, weight loss, hepatosplenomegaly, respiratory and digestive symptoms were present in 86.2%, 50%, 44.4% and 41.7% of the patients, respectively. At admission, 24 patients had low CD4 T-cell count and high viral load values. Among the 30 patients who received antifungals, 16 (53.3%) were cured, 13 (43.3%) died, and one was lost to follow-up. Six patients died prior to therapy. From 1990 to 2018, 63 necropsies of patients with Histoplasma capsulatum infection were performed. Of these patients, 29 (46.0%) were HIV-infected individuals, including 21 (72.4%) who presented disseminated histoplasmosis and 21 (72.4%) who were diagnosed with histoplasmosis at necropsy. The epidemiological, clinical and outcome profiles presented herein are similar to those described elsewhere and reinforce the difficulties that are still present in limited-resource settings where advanced immunodeficiency, combined with severe fungal infection and late patient admissions, is related to poor outcomes.
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http://dx.doi.org/10.1007/s11046-020-00435-yDOI Listing
April 2020

Effects of Exercise Training and Statin Use in People Living with Human Immunodeficiency Virus with Dyslipidemia.

Med Sci Sports Exerc 2020 01;52(1):16-24

Postgraduate Program in Health Science, Faculty of Medicine, Federal University of Uberlândia, Uberlândia/MG, BRAZIL.

Purpose: To evaluate the effects of the combination of exercise training (ET) and statins in people living with human immunodeficiency virus.

Methods: This was a randomized, double-blind, placebo-controlled clinical trial. Eighty-three people living with human immunodeficiency virus were assigned to either placebo (PL), statins (STA), PL + ET (PLET) or STA + ET (STAET) groups. Volunteers assigned to STA and STAET groups were administered 10 mg of rosuvastatin, whereas the PL and PLET groups were administered a placebo. The PLET and STAET groups performed ET three times a week. Before and after the 12-wk follow-up, the volunteers underwent to anthropometric assessment and blood collection to evaluate lipid profile, cardiovascular markers, inflammatory profile; a Doppler ultrasound examination, muscle strength (MS) and cardiorespiratory fitness (CF) tests were performed.

Results: There was a decrease in total cholesterol, triglycerides, low-density lipoprotein, C-reactive protein, fibrinogen, interleukin (IL)-1β and right carotid intima-media thickness in the STA, PLET, and STAET groups compared with PL group (P < 0.001). Furthermore, there was a decrease in total cholesterol, triglycerides, low-density lipoprotein, IL-1β, IL-6, and IL-8 levels and in left and right carotid intima-media thickness and an increase in HDL-c levels in the STAET groups compared with the STA (P ≤ 0.001) and PLET groups (P ≤ 0.001). There was an increase in IL-10 levels, peak-systolic velocity, end-diastolic velocity, wall shear rate in the PLET and STAET groups compared with the PL (P ≤ 0.001) and STA groups (P ≤ 0.001). The PLET and STAET groups reduced body fat mass, body fat percentage and increased lean body mass, MS and CF compared with PL (P ≤ 0.001) and STA (P ≤ 0.001) groups.

Conclusions: The combination of ET and statins is useful to enhance lipid and inflammatory profiles, reduce cardiovascular disease markers, and improve Doppler ultrasound findings, MS and CF in people living with HIV.
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http://dx.doi.org/10.1249/MSS.0000000000002120DOI Listing
January 2020

Main findings and diagnostic yield of bronchoalveolar lavage, bronchial brushing and transbronchial biopsy in HIV-positive patients.

Rev Inst Med Trop Sao Paulo 2019 25;61:e61. Epub 2019 Nov 25.

Universidade Federal do Triângulo Mineiro, Departamento de Clínica Cirúrgica, Uberaba, Minas Gerais, Brazil.

Bronchoalveolar lavage, bronchial brushing and transbronchial biopsy are of fundamental importance in the diagnosis of pathologies affecting the lungs of immunosuppressed patients, especially those infected with HIV. This was a descriptive and retrospective study, in which the results of bronchoalveolar lavages, bronchial brushings and transbronchial biopsies of HIV-positive patients attended at the Clinical Hospital of the Federal University of Triangulo Mineiro from 1999 to 2015 were reviewed to determine the most frequent findings in these patients, to evaluate the diagnostic accuracy of these procedures and to correlate bronchoscopy results with clinical and radiological findings. Serological tests for HIV were confirmed and cases with negative or unverified serology were excluded. Medical records were reviewed for correlation with clinical and radiological findings. A total of 1,423 patients with a mean age of 50 years were initially selected; 727 cases had no serology for HIV; 696 had serology for HIV and 64 were positive. Of these, 47 were men, aged 24 to 84 years, and 17 women, aged 31 to 69 years. Biopsies and cytological tests were positive in 20 (31.25%) of the 64 patients and the most frequent diagnosis was pneumocystosis, found in 8 cases (12.5%). Of the 20 bronchofibroscopy-positive patients, only 2 did not show agreement between histopathological and clinical-radiological diagnoses. The analysis of the cytological tests and biopsy specimens obtained by bronchofibroscopy seems to be valuable for the etiological diagnosis of pulmonary infections in HIV- positive patients; however, negative results do not always exclude the diagnosis. In these cases, clinical symptoms and imaging findings may help to guide the best therapy.
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http://dx.doi.org/10.1590/S1678-9946201961061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880975PMC
December 2019

Choroiditis in a HIV-infected patient with disseminated cryptococcal infection: A case report and literature review.

Rev Iberoam Micol 2019 Jul - Sep;36(3):155-159. Epub 2019 Oct 30.

Internal Medicine Department, Infectious Diseases Unit, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil. Electronic address:

Background: Ocular involvement in AIDS patients is a common event mainly caused by inflammation or infection. Despite the high prevalence rate of cryptococcosis in these individuals, ocular features have been occasionally described.

Case Report: A 20-year-old Brazilian female with HIV infection recently diagnosed was admitted with a respiratory profile presumptively diagnosed as Pneumocystis jirovecii pneumonia; an ophthalmologic exam suggested choroiditis by this agent as well. She was complaining of headaches and blurred vision which led to cryptococcal meningitis diagnosis by a CSF positive India ink stain and Cryptococcus neoformans positive culture. Despite therapy based on amphotericin B plus fluconazole, her clinical state progressively worsened and the patient died one week later. At necropsy, disseminated cryptococcal infection was evidenced in several organs including eyes, which presented bilateral chorioretinitis.

Conclusions: Cryptococcal ocular involvement in AIDS patients has been occasionally proved among the cases already reported. Thus, the post mortem exam is still pivotal to improve the quality of the clinical diagnosis, especially in limited-resource settings.
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http://dx.doi.org/10.1016/j.riam.2019.04.004DOI Listing
May 2020

Subclinical Carotid Atherosclerosis and Reduced DAD Score for Cardiovascular Risk Stratification in HIV-Positive Patients.

Arq Bras Cardiol 2020 01;114(1):68-75

Universidade Federal do Triangulo Mineiro, Uberaba, MG - Brazil.

Background: HIV-positive patients are twice as likely than the general population to have a heart attack and are four times at greater risk of sudden death. In addition to the increased risk, these individuals present with cardiovascular events on average approximately 10 years earlier than the general population.

Objective: To compare Framingham and reduced DAD (Data Collection on Adverse Effects of Anti-HIV Drugs Cohort) scores for cardiovascular risk assessment in HIV-positive patients and potential impact on clinical decision after evaluation of subclinical carotid atherosclerosis.

Methods: Seventy-one HIV-positive patients with no history of cardiovascular disease were clinically evaluated, stratified by the Framingham 2008 and reduced DAD scores and submitted to subclinical carotid atherosclerosis evaluation. Agreement between scores was assessed by Kappa index and p < 0.05 was considered statistically significant.

Results: mean age was 47.2 and 53.5% among males. The rate of subclinical atherosclerosis was 39.4%. Agreement between scores was 49% with Kappa of 0.735 in high-risk patients. There was no significant difference between scores by ROC curve discrimination analysis. Among patients with intermediate risk and Framingham and reduced DAD scores, 62.5% and 30.8% had carotid atherosclerosis, respectively.

Conclusion: The present study showed a correlation between the scores and medium-intimal thickening, besides a high correlation between patients classified as high risk by the Framingham 2008 and reduced DAD scores. The high prevalence of carotid atherosclerosis in intermediate risk patients suggests that most of them could be reclassified as high risk.
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http://dx.doi.org/10.5935/abc.20190227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025314PMC
January 2020

Clinical and anatomopathological aspects of patients with hantavirus cardiopulmonary syndrome in Uberaba, Minas Gerais, Brazil.

Rev Inst Med Trop Sao Paulo 2019 10;61:e55. Epub 2019 Oct 10.

Universidade Federal do Triângulo Mineiro, Departamento de Clínica Cirúrgica, Uberaba, Minas Gerais, Brazil.

The hantavirus cardiopulmonary syndrome is considered an emerging disease in the Americas. Since 1993, thousands of cases have been reported from different countries, but mainly from Brazil. This study aims to describe some epidemiological, clinical and anatomopathological aspects of patients with hantavirus who presented poor outcome and were autopsied in a teaching hospital in Brazil, from 2000 to 2014. Of the 10 patients included, nine were male (mean age 43.5 years) and seven reported previous contact with rodents. Fever was present in eight of ten patients, dyspnea in nine of ten and myalgia in seven of ten patients; hemoconcentration, leukocytosis, thrombocytopenia and renal involvement were evidenced in all the 10 cases. At autopsy, the main alterations were seen in the lungs: pleural effusion (8/10 cases), increased weight 2.5 to 3 times, congestion/edema (10/10), interstitial mononuclear inflammation (10/10), alveolar hemorrhage (7/10), pulmonary collapse (7/10), hyaline membranes (7/10) and alveolar neutrophilic infiltrate (2/10). Pericardial effusion (2/10), mild myocardium inflammation (4/10), right ventricle dilation (1/10), polyploidy nuclei (3/10) and pericardial diffuse petechial (1/10) were also observed. The other organs exhibited discrete and non-specific alterations. Currently, this syndrome continues to be associated with high mortality directly linked to a late diagnosis and/or a misdiagnosis in the medical centers where these patients were seen for the first time. The anatomopathological findings at autopsy revealed the final phase of the process with pulmonary alterations, allowing a direct correlation with the severity of respiratory distress observed in these patients at admission.
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http://dx.doi.org/10.1590/S1678-9946201961055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792360PMC
October 2019

Epidemiological, Clinical and Outcome Aspects of Patients with Cryptococcosis Caused by Cryptococcus gattii from a Non-endemic Area of Brazil.

Mycopathologia 2019 Feb 10;184(1):65-71. Epub 2018 Nov 10.

Internal Medicine Department, Infectious Diseases Unit, Triângulo Mineiro Federal University, Medicina Tropical, Caixa Postal 118, Uberaba, Minas Gerais, CEP 38001-170, Brazil.

Cryptococcosis by Cryptococcus gattii occurs mainly in immunocompetent hosts, however, during the last decades, a growing number of cases in immunocompromised individuals have been noticed around the world. This report presents epidemiological, clinical and outcome aspects of patients with cryptococcosis caused by this species from a non-endemic area in Brazil. Of 278 Cryptococcus spp. clinical isolates recovered during the same period, 267 (96%) were molecularly identified as Cryptococcus neoformans VNI genotype and 11 (4%) as C. gattii VGII genotype by URA-5 RFLP. Of the 11 C. gattii patients, eight were male, mean age of 47.5 years. Of these, four were HIV-infected, one was kidney transplanted, one presented low CD4 T cells values of unknown cause, another presented chronic liver disease meanwhile the remaining four were apparently immunocompetent. Disseminated disease and cryptococcal meningitis were present in four patients each. Most patients received amphotericin B plus fluconazole. Seven out of the 11 patients cured and four died before or during the therapy. The increased number of individuals with cryptococcosis by this species during the last decades needs to be carefully evaluated specially those who are HIV-infected. Nevertheless, Cryptococcus species differentiation is currently relevant in order to better know their relation with geographical, clinical host preference and outcome particularities.
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http://dx.doi.org/10.1007/s11046-018-0304-3DOI Listing
February 2019

[Brazilian guidelines for the clinical management of paracoccidioidomycosis].

Epidemiol Serv Saude 2018 08 16;27(spe):e0500001. Epub 2018 Aug 16.

Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brasil.

Paracoccidioidomycosis is a systemic fungal disease associated with agricultural activities. Its incidence and prevalence are underestimated because of the lack of reporting in several Brazilian states. If paracoccidiodomycosis is not diagnosed and treated early and adequately, endemic fungal infection may result in serious sequelae. In addition to the Paracoccidioides brasiliensis (P. brasiliensis) complex, the appearance of a new species, Paracoccidioides lutzii (P. lutzii), in Rondônia state, where the disease has reached epidemic levels, and in the country's Midwest region and Pará state, are challenges to diagnosis and to the urgent availability of antigens that are reactive with patients' sera. These guidelines aim to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. The guidelines provide data on etiology, epidemiology, immunopathogenesis, diagnosis, treatment and sequelae, with emphasis on diagnosis and treatment, as well as current recommendations and challenges in this field of knowledge.
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http://dx.doi.org/10.5123/S1679-49742018000500001DOI Listing
August 2018

Genotypic analysis of clinical and environmental Cryptococcus neoformans isolates from Brazil reveals the presence of VNB isolates and a correlation with biological factors.

PLoS One 2018 5;13(3):e0193237. Epub 2018 Mar 5.

Infectious Disease Department, Triangulo Mineiro Federal University, Uberaba, Brazil.

Cryptococcal infections are mainly caused by members of the Cryptococcus neoformans species complex (molecular types VNI, VNII, VNB, VNIV and the AD hybrid VNIII). PCR of the mating type loci and MLST typing using the ISHAM-MLST consensus scheme were used to evaluate the genetic relationship of 102 (63 clinical and 39 environmental) C. neoformans isolates from Uberaba, Brazil and to correlate the obtained genotypes with clinical, antifungal susceptibility and virulence factor data. All isolates were mating type alpha. MLST identified 12 known and five new sequence types (ST). Fourteen STs were identified within the VNI isolates, with ST93 (57/102, 56%) and ST77 (19/102, 19%) being the most prevalent. From the nine VNII isolates previously identify by URA5-RFLP only four (ST40) were confirmed by MLST. The remaining five grouped within the VNB clade in the phylogenetic analysis corresponding to the sequence type ST504. Other two environmental isolates also grouped within VNB clade with the new sequence type ST527. The four VNII/ST40 isolates were isolated from CSF. The two VNIV sequence types (ST11 and ST160) were isolated from blood cultures. Two of six patients evaluated with more than one isolates had mixed infections. Amongst the VNI isolates 4 populations were identified, which showed differences in their susceptibility profiles, clinical outcome and virulence factors. These results reinforce that ST93 is the most prevalent ST in HIV-infected patients in the Southeastern region of Brazil. The finding of the VNB molecular type amongst environmental Brazilian isolates highlights that this genotype is not restricted to the African continent.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193237PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837091PMC
July 2018

Brazilian guidelines for the clinical management of paracoccidioidomycosis.

Rev Soc Bras Med Trop 2017 Sep-Oct;50(5):715-740. Epub 2017 Jul 12.

Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.

Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients' sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.
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http://dx.doi.org/10.1590/0037-8682-0230-2017DOI Listing
December 2017

Cytokine patterns in a prospective cohort of HIV-infected patients with cryptococcal meningitis following initiation of antifungal and antiretroviral therapy.

PLoS One 2017 9;12(5):e0176304. Epub 2017 May 9.

Infectious Diseases Unit, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.

Cryptococcal meningitis (CM) is a life-threatening infection in HIV-infected patients, especially in resource-limited settings. Cytokine patterns in the cerebrospinal fluid (CSF) and sera may be related to clinical outcomes. This study aimed to evaluate cytokine patterns in the CSF and sera of HIV-infected patients with CM as well as the cytokines produced by peripheral blood mononuclear cells (PBMCs) when stimulated with LPS and cryptococcal GXM. CSF and serum levels of IL-2, IL-4, IL-8, IL-10, IL-12p40, IL-17A, INF-γ, TNF-α and CXCL-10 were measured in HIV-infected patients with CM (CM+ HIV+) at various time points. Cytokine levels were evaluated in the PBMC culture supernatants and the baseline values were compared to those of HIV-infected patients without CM (CM- HIV+) and healthy controls (CM- HIV-). CSF cytokine levels at admission (n = 33) were higher than levels among the 23 survivors at week 2, but statistically significant differences were observed for IL-8 and IFN-γ (p<0.05). CSF and serum levels of IL-4 and IL-17A at week 10 (n = 16) were lower than the baseline values, whereas IL-2 levels increased compared to week 2 (p<0.05). At week 16 (n = 15), CSF and serum levels of IL-4, IL-10 and CXCL-10 were decreased compared to the baseline values (p<0.05). PBMCs from CM- HIV- individuals produced significantly higher levels of proinflammatory cytokines in response to LPS, with the exception of TNF-α, which showed higher levels among CM+ HIV+ patients. The PBMCs of CM patients produced higher levels of IL-4 than those of CM- HIV- patients in response to GXM stimulation, and levels progressively decreased during treatment (p<0.05). Then, a progressive shift in cytokine expression favoring a Th1 pattern was observed, which is crucial in controlling cryptococcal infection. A better understanding of the protective immune response against Cryptococcus neoformans will help to develop novel strategies to improve the outcomes of patients with cryptococcosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176304PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423598PMC
September 2017

Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy).

Rev Inst Med Trop Sao Paulo 2017 Apr 3;59:e3. Epub 2017 Apr 3.

Universidade Federal do Triângulo Mineiro, Departamento de Patologia Especial, Uberaba, Minas Gerais, Brazil.

Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases); B - one or two antiretroviral drugs or HAART for less than six months (83 cases); C - HAART for six months or longer (54 cases). In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%), followed by cytomegalovirus (19.2%), Histoplasma capsulatum (6.5%), mycobacteria (5.6%), and Toxoplasma gondii (4.3%). T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV) was more frequent in group A compared with groups B and C (p < 0.05); 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.
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http://dx.doi.org/10.1590/S1678-9946201759003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441154PMC
April 2017

Paracoccidioidomycosis in Brazilian Patients With and Without Human Immunodeficiency Virus Infection.

Am J Trop Med Hyg 2017 02 28;96(2):368-372. Epub 2016 Nov 28.

Infectious Diseases Unit, Internal Medicine Department, Triângulo Mineiro Federal University, Uberaba, Brazil.

Paracoccidioidomycosis (PCM) is endemic to Latin America, where 10 million people may be infected with / and 1,600,000 individuals live with human immunodeficiency virus (HIV) infection. An epidemiological overlapping of these infections occurred early in acquired immunodeficiency syndrome era with nearly 180 published cases. This study presents epidemiological, clinical, and outcome profiles for 31 PCM patients with HIV infection diagnosed in a teaching hospital in Brazil, and includes an update of previously reported cases. Medical records were reviewed and data compared with 64 PCM patients without HIV infection. Of the 31 PCM patients with HIV infection, 23 (74.1%) were male, with a median age of 36.7 years, whereas of the 64 PCM, 45 (70.3%) were male, with a median age of 35.1 years. Both groups presented similar proportions for smoking and alcoholism. PCM patients with HIV infection presented more fever, weight loss, and the acute clinical form than the PCM patients who had more mucosal and respiratory involvement characterizing the chronic form. Most PCM patients with HIV infection exhibited overlapping symptoms from both clinical forms with median symptom duration of 4.5 months compared with 8.3 months for the PCM control. Patients received sulfonamides and/or itraconazole for a median of 15.7 and 16.7 months for PCM/HIV-infected and PCM, respectively. Relapses occurred more in PCM (12 [30%]) than PCM/HIV-infected (4 [14.8%]) patients, whose mortality rate was higher (10 [32.8%]) than PCM patients (8 [20%]). The cases of PCM/HIV infection confirm that HIV can interact with some endemic diseases without increasing their frequency, while changing their natural history, clinical presentation, and outcome. The data presented here are in agreement with those observed in other studies.
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http://dx.doi.org/10.4269/ajtmh.16-0254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303038PMC
February 2017

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil.

Am J Trop Med Hyg 2016 10 25;95(4):781-785. Epub 2016 Jul 25.

Infectious Diseases Unit, Triângulo Mineiro Federal University, Minas Gerais, Brazil.

Cryptococcosis occurs in acquired immunodeficiency syndrome (AIDS) patients with poor compliance to antiretroviral therapy or unaware of their human immunodeficiency virus status who present severe immunosuppression at admission. Consequently, high mortality rates are observed due to disseminated fungal infection. This report presents clinical and postmortem data of AIDS patients with cryptococcosis in a teaching hospital in Brazil. Retrospectively, medical and necropsy records of AIDS patients with cryptococcosis clinically confirmed and/or postmortem verified were reviewed. Clinical data were compared with those of patients presenting a good outcome to evaluate disseminated fungal infection and the agreement between clinical and postmortem diagnosis. At admission, most of the 45 patients with cryptococcal meningitis who died, presented more altered consciousness (P = 0.0047), intracranial increased pressure (P = 0.047), and severe malnutrition (P = 0.0006) than the survivors. Of 29 (64.4%) patients with cryptococcal meningitis, 23 died before week 2 on antifungal therapy, and the other six during the next 3 months. The remaining 16 (35.6%) cases had other diagnoses and died soon after. At necropsy, 31 (68.9%) presented disseminated infection involving two or more organs, whereas 14 (31.1%) cases had meningeal or pulmonary localized infection. The agreement of 64.4% between clinical and postmortem diagnosis was similar to some studies. However, other reports have shown figures ranging from 34% to 95%. Currently, a progressive worldwide decrease of autopsies is worrying because the role of postmortem examination is pivotal to verify or identify the death causes, which contributes to improve the quality of clinical diagnosis and medical training.
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http://dx.doi.org/10.4269/ajtmh.16-0148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062772PMC
October 2016

Non-linear resistance training reduces inflammatory biomarkers in persons living with HIV: A randomized controlled trial.

Eur J Sport Sci 2016 Nov 30;16(8):1232-9. Epub 2016 Mar 30.

a Postgraduate Program in Physical Education , Federal University of Triângulo Mineiro , Uberaba , MG , Brazil.

The purpose of this study is to analyse the effect of 12 weeks of non-linear resistance training (NLRT) on anthropometry, muscle strength and inflammatory biomarkers in persons infected with human immunodeficiency virus (PIHIV). Thirty previously sedentary PIHIVs were randomized into the NLRT (n = 15) and control (CON, n = 15) groups. NLRT group were submitted to 12 weeks of training, whereas the CON group maintained their daily habits. At baseline and after 12 weeks, both groups underwent anthropometric evaluations and blood sampling for the analysis of inflammatory biomarkers. Analysis of covariance using preintervention values as covariate was performed to determine the effects of exercise on anthropometry, muscle strength, cytokines levels and T cells. Significance was set at p < 0.05. After 12 weeks of intervention, there was a decrease in subcutaneous body fat (p < .0001), neck, abdomen and waist circumferences (p < .05), waist-to-hip ratio (p = .009), blood levels of interleukin (IL)-1β (p = .029), IL-6 (p = .005), IL-8 (p = .010), and tumour necrosis factor (TNF)-α (p = .001) and an increase in muscle strength (p < .0001), IL-10 levels (p = .030) and CD4(+) (p = .004) and CD8(+) (p < .0001) counts in the NLRT compared to CON group. Twelve weeks of NLRT promoted positive changes in the body fat, body circumferences, muscular strength and inflammatory profile in PIHIV.
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http://dx.doi.org/10.1080/17461391.2016.1167962DOI Listing
November 2016

Nonlinear Resistance Training Enhances the Lipid Profile and Reduces Inflammation Marker in People Living With HIV: A Randomized Clinical Trial.

J Phys Act Health 2016 07 19;13(7):765-70. Epub 2016 Feb 19.

Post-Graduate Program in Physical Education, Federal University of Triângulo Mineiro, Uberaba/MG, Brazil.

Background: Highly active antiretroviral therapy (HAART) is associated with high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), triglyceride (TG), and C-reactive protein (CRP) levels. The natural course of the HIV infection reduces the high-density lipoprotein level (HDL-c). Thus, physical exercise plays a key role in reducing the effects of HAART and HIV.

Methods: Thirty people living with HIV (PLHIV) were randomized to the nonlinear resistance training (NLRT) and control (CON) groups. The NLRT group underwent 12 weeks of resistance training, whereas the CON group maintained usual daily activities. All volunteers underwent anthropometric, body composition, and biochemical assessments at the beginning and end of 12 weeks.

Results: After 12 weeks, the NLRT group had increased lean body mass (P < .0001), and a reduction in body fat mass (P < .0001) and body fat percentage (P < .0001). The levels of TC (P < .0001), LDL-c (P = .049), TG (P < .0001), and CRP (P = .004) were reduced, and the HDL-c level increased (P < .0001).

Conclusion: Twelve weeks of NLRT causes beneficial changes in the body composition, lipid profile, and inflammation markers in PLHIV, and it can be used in this patient population.
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http://dx.doi.org/10.1123/jpah.2015-0540DOI Listing
July 2016

High interleukin-4 expression and interleukin-4 gene polymorphisms are associated with susceptibility to human paracoccidioidomycosis.

Mem Inst Oswaldo Cruz 2015 Sep;110(6):781-5

Laboratório de Imunologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brasil.

Paracoccidioidomycosis (PCM) is caused by dimorphic fungi from the Paracoccidioides brasiliensis complex. Previous studies have demonstrated that the severity of disease is associated with a T-helper 2 immune response characterised by high interleukin (IL)-4 production. In the present study we analysed two polymorphisms in the IL-4 gene (-590 C/T and intron-3 microsatellite) in 76 patients with PCM and 73 control subjects from an endemic area. The production of IL-4 by peripheral blood mononuclear cells after antigen or phytohaemagglutinin stimulation was determined by ELISA. A significant correlation was observed between the RP2/RP2 intron-3 genotype and infection with Paracoccidioides sp.(p = 0.011), whereas the RP1/RP1 genotype was correlated with resistance. No significant correlation was observed for the IL-4 promoter polymorphism. Furthermore, the low IL-4 expression observed in the control group compared with patients was associated with the RP1/RP1 genotype. These results suggest that IL-4 polymorphisms might be associated with the ability of the host to control Paracoccidioides sp.infection. The relevance of this polymorphism is supported by the observation that patients with disease produce high levels of IL-4 following mitogen or antigen stimulation. The IL-4 gene is located in the cytokine cluster region of chromosome 5 where other polymorphisms have also been described.
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http://dx.doi.org/10.1590/0074-02760150197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667581PMC
September 2015

Species Distribution, Virulence Factors, and Antifungal Susceptibility Among Candida parapsilosis Complex Isolates Recovered from Clinical Specimens.

Mycopathologia 2015 Dec 3;180(5-6):333-43. Epub 2015 Jul 3.

Laboratório de Microbiologia, Departamento de Microbiologia, Imunologia e Parasitologia, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Praça Manoel Terra 330, Uberaba, Minas Gerais, 38025-015, Brazil.

The Candida parapsilosis complex has emerged as an important fungal pathogen. In spite of this, relatively little is known about its characteristics. Thus, the purposes of this study were (1) to determine by BanI-RFLP-assay the occurrence of C. parapsilosis complex species among 81 clinical isolates primarily identified as C. parapsilosis; (2) to evaluate their in vitro production of virulence factors; and (3) to compare their susceptibility profiles, grown as planktonic cells and biofilms, against amphotericin B, fluconazole, voriconazole, and caspofungin by following the Clinical and Laboratory Standards Institute (CLSI) guidelines. Seventy-seven isolates (95%) were identified as C. parapsilosis sensu stricto, 2 (2.5%) as C. orthopsilosis, and 2 (2.5%) as C. metapsilosis. Protease activity was detected in 29 (37.7%) isolates of C. parapsilosis sensu stricto, whereas only 7 (9.1%) exhibited phospholipase activity. None of the C. metapsilosis or C. orthopsilosis was able to produce protease or phospholipase. Biofilm production was detected in 35 (43.2%) isolates, among which 33 were C. parapsilosis sensu stricto and 2 were C. orthopsilosis. Antifungal resistance was uncommon; only one C. metapsilosis was fluconazole resistant. However, biofilm-producing isolates showed a marked resistance to all antifungal agents tested, particularly to voriconazole. This knowledge could be of clinical relevance for guiding therapeutic decisions.
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http://dx.doi.org/10.1007/s11046-015-9916-zDOI Listing
December 2015

Cytokine profiles at admission can be related to outcome in AIDS patients with cryptococcal meningitis.

PLoS One 2015 23;10(3):e0120297. Epub 2015 Mar 23.

Infectious Diseases Unit, Internal Medicine Department, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.

Cryptococcal meningitis (CM) remains as common life-threatening AIDS-defining illness mainly in resource-limited settings. Previous reports suggested that baseline cytokine profiles can be associated to fungal burden and clinical outcome. This study aimed to evaluate the baseline cytokine profiles in AIDS patients with CM and its relation with the outcome at weeks 2 and 10. Thirty AIDS patients with CM diagnosed by cerebrospinal fluid (CSF) Cryptococcus neoformans positive culture, India ink stain and cryptococcal antigen test were prospectively evaluated. As controls, 56 HIV-infected patients without CM and 48 non-HIV individuals were included. Baseline CSF and sera levels of IL-2, IL-4, IL-8, IL-10, IL-12p40, IL-17A, INF-γ and TNF-α were measured by ELISA. Of 30 CM patients, 24 (80%) were male, median age of 38.1. The baseline CSF high fungal burden and positive blood culture were associated with a positive CSF culture at week 2 (p = 0.043 and 0.029). Most CSF and sera cytokines presented higher levels in CM patients than control subjects (p < 0.05). CSF levels of IL-8, IL-12p40, IL-17A, TNF-α, INF-γ and sera TNF-α were significantly higher among survivors at weeks 2 and 10 (p < 0.05). Patients with increased intracranial pression exhibited CSF IL-10 high levels and poor outcome at week 10 (p = 0.032). Otherwise, baseline CSF log10 IFN-γ and IL-17A were negatively correlated with fungal burden (r = -0.47 and -0.50; p = 0.0175 and 0.0094, respectively). The mortality rate was 33% (10/30) at week 2 and 57% (17/30) at week 10. The severity of CM and the advanced immunodeficiency at admission were related to a poor outcome in these patients. Otherwise, the predominant Th1 cytokines profile among survivors confirms its pivotal role to infection control and would be a prognostic marker in cryptococcal meningitis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370646PMC
December 2015

Phylogenetic analysis of phenotypically characterized Cryptococcus laurentii isolates reveals high frequency of cryptic species.

PLoS One 2014 24;9(9):e108633. Epub 2014 Sep 24.

Department of Infectious and Parasitic Diseases, Triangulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.

Background: Although Cryptococcus laurentii has been considered saprophytic and its taxonomy is still being described, several cases of human infections have already reported. This study aimed to evaluate molecular aspects of C. laurentii isolates from Brazil, Botswana, Canada, and the United States.

Methods: In this study, 100 phenotypically identified C. laurentii isolates were evaluated by sequencing the 18S nuclear ribosomal small subunit rRNA gene (18S-SSU), D1/D2 region of 28S nuclear ribosomal large subunit rRNA gene (28S-LSU), and the internal transcribed spacer (ITS) of the ribosomal region.

Results: BLAST searches using 550-bp, 650-bp, and 550-bp sequenced amplicons obtained from the 18S-SSU, 28S-LSU, and the ITS region led to the identification of 75 C. laurentii strains that shared 99-100% identity with C. laurentii CBS 139. A total of nine isolates shared 99% identity with both Bullera sp. VY-68 and C. laurentii RY1. One isolate shared 99% identity with Cryptococcus rajasthanensis CBS 10406, and eight isolates shared 100% identity with Cryptococcus sp. APSS 862 according to the 28S-LSU and ITS regions and designated as Cryptococcus aspenensis sp. nov. (CBS 13867). While 16 isolates shared 99% identity with Cryptococcus flavescens CBS 942 according to the 18S-SSU sequence, only six were confirmed using the 28S-LSU and ITS region sequences. The remaining 10 shared 99% identity with Cryptococcus terrestris CBS 10810, which was recently described in Brazil. Through concatenated sequence analyses, seven sequence types in C. laurentii, three in C. flavescens, one in C. terrestris, and one in the C. aspenensis sp. nov. were identified.

Conclusions: Sequencing permitted the characterization of 75% of the environmental C. laurentii isolates from different geographical areas and the identification of seven haplotypes of this species. Among sequenced regions, the increased variability of the ITS region in comparison to the 18S-SSU and 28S-LSU regions reinforces its applicability as a DNA barcode.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108633PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177401PMC
December 2015

Central nervous system paracoccidioidomycosis in an AIDS patient: case report.

Mycopathologia 2014 Feb 24;177(1-2):137-41. Epub 2014 Jan 24.

Infectious Diseases Unit, Triângulo Mineiro Federal University, Avenida Frei Paulino, 30, Uberaba, Minas Gerais, CEP 38025-180, Brazil,

Up to now, over 200 patients with paracoccidioidomycosis (PCM) associated to HIV infection have already been reported; however, the central nervous system involvement in this coinfection was rarely reported. This paper presents a 35-year-old Brazilian male AIDS patient who developed pulmonary PCM successfully treated with itraconazole. At the antiretroviral therapy starting, he had 32 CD4(+) T cells baseline count and high viral load levels. After 9 months, he presented severe fungal meningoencephalitis diagnosed by sublenticular enhanced nodular lesion at computerized tomography and magnetic resonance brain imaging and a positive Paracoccidiodes brasiliensis smear and culture from cerebrospinal fluid. At the time, a sixfold increase in CD4(+) T cell count and undetectable viral load level were evidenced. The patient received amphotericin B during 1 year presenting slow but progressive clinical improvement, and he is currently asymptomatic and without neurological disabilities. To our knowledge, this is the second case report of a patient with neuroparacoccidioidomycosis associated to HIV infection.
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http://dx.doi.org/10.1007/s11046-014-9729-5DOI Listing
February 2014

Susceptibility profile of clinical and environmental isolates of Cryptococcus neoformans and Cryptococcus gattii in Uberaba, Minas Gerais, Brazil.

Med Mycol 2013 Aug 23;51(6):635-40. Epub 2013 Jan 23.

Infectious Diseases Unit, Triangulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.

Cryptococcus neoformans and C. gattii are the etiologic agents of cryptococcosis, a life-threatening disease in both immunocompromised and immunocompetent hosts. Antifungal resistance has been evaluated using different methods, breakpoints, and sizes of test populations and it is an emerging as a significant issue worldwide. A total of 176 (95 clinical and 81 environmental) C. neoformans and eight clinical C. gattii isolates were evaluated to determine the minimal inhibitory concentration (MIC) according to the Clinical and Laboratory Standards Institute method. A total of 10.5% of the C. neoformans clinical isolates were resistant to amphotericin B (AMB), and 6.2% of the environmental isolates were resistant to fluconazole (FLZ). Environmental and clinical isolates presented epidemiologic cut-off values (ECVs) of 64 and 16 to FLZ and 1 and 2 to AMB, respectively. All of the C. gattii isolates showed high susceptibility to most drugs evaluated. Clinical isolates had lower susceptibility than environmental isolates to AMB and itraconazole whereas environmental isolates had lower susceptibility than the clinical isolates to FLZ, voriconazole, and ketoconazole. However, no difference was found in the susceptibility of the two species. The MICs and ECVs to antifungals can help to select the best therapeutic option for tracking epidemiological resistance among clinical and environmental isolates of Cryptococcus spp. around the world.
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http://dx.doi.org/10.3109/13693786.2012.761737DOI Listing
August 2013

Morphological changes in the digestive system of 93 human immunodeficiency virus positive patients: an autopsy study.

Rev Inst Med Trop Sao Paulo 2012 Mar-Apr;54(2):89-93

Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.

Involvement of the digestive system in patients with acquired immunodeficiency syndrome (AIDS) is frequent and many changes in these patients are diagnosed only at autopsy. There are few studies of autopsy with detailed analysis of this system and only one was conducted in Brazil. We evaluated each segment of the digestive system in 93 consecutive autopsies of patients infected with human immunodeficiency virus (HIV) and the importance of these lesions to death. Of these, 90 (96.8%) patients had AIDS. We reviewed medical records, autopsy reports and histological sections from tongue to rectum stained with hematoxylin-eosin. When necessary, we analyzed special stains and immunohistochemistry to investigate infections. There was damage to the digestive system in 73 (78.5%) cases. The most common infections were candidiasis (42%), cytomegalovirus (29%), histoplasmosis (11.8%), toxoplasmosis (9.7%) and mycobacterial infection (9.7%). Malignancies were rare, present in four (4.3%) cases (two Kaposi's sarcoma, one adenocarcinoma and one metastatic embryonal carcinoma). All segments showed lesions: tongue (48.6%), esophagus (44.8%), stomach (44.7%), colon (43.2%) and small intestine (28.9%). The lesions found were immediate cause of death in five (5.4%) cases. In another 36 (38.7%) cases the basic disease was systemic and also compromised the digestive system.
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http://dx.doi.org/10.1590/s0036-46652012000200006DOI Listing
September 2012

Neuropathology of AIDS: An Autopsy Review of 284 Cases from Brazil Comparing the Findings Pre- and Post-HAART (Highly Active Antiretroviral Therapy) and Pre- and Postmortem Correlation.

AIDS Res Treat 2012 22;2012:186850. Epub 2012 Feb 22.

Discipline of Special Pathology, Universidade Federal do Triângulo Mineiro (UFTM), Avenida Getúlio Guaritá 130, 38025-440 Uberaba, MG, Brazil.

A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989-2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies.
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http://dx.doi.org/10.1155/2012/186850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296154PMC
August 2012

Disseminated Sporothrix brasiliensis infection with endocardial and ocular involvement in an HIV-infected patient.

Am J Trop Med Hyg 2012 Mar;86(3):477-80

Infectious and Parasitic Diseases Unit, Hospital de Clínicas, Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.

Disseminated sporotrichosis occurs in individuals with impaired cellular immunity, such as in cases of neoplasia, transplantation, diabetes, and especially, acquired immunodeficiency syndrome. This report presents a 32-year-old Brazilian human immunodeficiency virus (HIV)-infected patient who developed a protracted condition of disseminated sporotrichosis with endocarditis, bilateral endophthalmitis, and lymphatic involvement. He needed cardiac surgery to replace the mitral valve. Sporothrix brasiliensis isolates were recovered from cultures of subcutaneous nodules and mitral valve fragments. Species identification was based on classical and molecular methods. The patient received amphotericin B for 52 days and subsequently, oral itraconazole. He remains asymptomatic, and he is on maintenance therapy with itraconazole. Despite his positive clinical outcome, he developed bilateral blindness. To our knowledge, this case is the first report of endocarditis and endophthalmitis caused by S. brasiliensis.
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http://dx.doi.org/10.4269/ajtmh.2012.11-0441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284366PMC
March 2012