Design of a Multi-Epitope Vaccine against Histoplasma capsulatum through Immunoinformatics Approaches.

Histoplasmosis is a widespread systemic disease caused by Histoplasma capsulatum, prevalent in the Americas. Despite its significant morbidity and mortality rates, no vaccines are currently available. Previously, five vaccine targets and specific epitopes for H. capsulatum were identified. Immunoinformatics has emerged as a novel approach for determining the main immunogenic components of antigens through in silico methods. Therefore, we predicted the main helper and cytotoxic T lymphocytes and B-cell epitopes for these targets to create a potential multi-epitope vaccine known as HistoVAC-TSFM. A total of 38 epitopes were found: 23 common to CTL and B-cell responses, 11 linked to HTL and B cells, and 4 previously validated epitopes associated with the B subunit of cholera toxin, a potent adjuvant. In silico evaluations confirmed the stability, non-toxicity, non-allergenicity, and non-homology of these vaccines with the host. Notably, the vaccine exhibited the potential to trigger both innate and adaptive immune responses, likely involving the TLR4 pathway, as supported by 3D modeling and molecular docking. The designed HistoVAC-TSFM appears promising against Histoplasma, with the ability to induce important cytokines, such as IFN-γ, TNF-α, IL17, and IL6. Future studies could be carried out to test the vaccine's efficacy in in vivo models.

Genotyping Analysis of Cryptococcus deuterogattii and Correlation with Virulence Factors and Antifungal Susceptibility by the Clinical and Laboratory Standards Institute and the European Committee on Antifungal Susceptibility Testing Methods.

Data about the relationship between their molecular types, virulence factors, clinical presentation, antifungal susceptibility profile, and outcome are still limited for Cryptococcus deuterogattii. This study aimed to evaluate the molecular and phenotypic characteristics of 24 C. deuterogattii isolates from the southeast region of Brazil. The molecular characterization was performed by multilocus sequence typing (MLST). The antifungal susceptibility profile was obtained according to CLSI-M27-A3 and EUCAST-EDef 7.1 methods. The virulence factors were evaluated using classic techniques. The isolates were divided into four populations. The molecular analysis suggests recombinant events in most of the groups evaluated. Resistance and susceptibility dose-dependent to fluconazole were evidenced in four isolates (16%) by EUCAST and in four isolates (16%) by CLSI methods. The agreement at ±two dilutions for both methods was 100% for itraconazole, ketoconazole, and voriconazole, 96% for amphotericin B, and 92% for fluconazole. Significant differences in virulence factor expression and antifungal susceptibility to itraconazole and amphotericin B were found. The mixed infection could be suggested by the presence of variable sequence types, differences in virulence factor production, and decreased antifungal susceptibility in two isolates from the same patient. The data presented herein corroborate previous reports about the molecular diversity of C. deuterogattii around the world.

Compartment Syndrome Secondary to Bothrops spp. Envenomation in Triângulo Mineiro, Region, Minas Gerais, Brazil.

BACKGROUND: Snakebite is a neglected global health problem with high morbidity. We describe compartment syndrome (CS) cases related to snakebites by Bothrops spp. METHODS: The medical records of patients admitted with snakebites envenomation were reviewed. RESULTS: Of 47 patients with Bothrops spp. envenomation (4 male; mean age: 42 years), 7 (15%) developed CS. The mean time to antivenom administration was 9.5 hours. The time to fasciotomy was variable. Seven patients developed infection and four had acute kidney injury. CONCLUSIONS: The incidence of CS is higher than that reported previously. This may be due to the clinical severity and long delay before administering antivenom.

Comparative Genomics of Histoplasma capsulatum and Prediction of New Vaccines and Drug Targets.

Histoplasma capsulatum is a thermodymorphic fungus that causes histoplasmosis, a systemic mycosis that presents different clinical manifestations, ranging from self-limiting to acute lung infection, chronic lung infection and disseminated infection. Usually, it affects severely immunocompromised patients although immunocompetent patients can also be infected. Currently, there are no vaccines to prevent histoplasmosis and the available antifungal treatment presents moderate to high toxicity. Additionally, there are few options of antifungal drugs. Thus, the aim of this study was to predict possible protein targets for the construction of potential vaccine candidates and predict potential drug targets against H. capsulatum. Whole genome sequences from four previously published H. capsulatum strains were analyzed and submitted to different bioinformatic approaches such as reverse vaccinology and subtractive genomics. A total of four proteins were characterized as good protein candidates (vaccine antigens) for vaccine development, three of which are membrane-bound and one is secreted. In addition, it was possible to predict four cytoplasmic proteins which were classified as good protein candidates and, through molecular docking performed for each identified target, we found four natural compounds that showed favorable interactions with our target proteins. Our study can help in the development of potential vaccines and new drugs that can change the current scenario of the treatment and prevention of histoplasmosis.

Effects of combination of Cryptococcus gattii and IFN-γ, IL-4 or IL-27 on human bronchial epithelial cells.

BACKGROUND: Airway epithelial cells are crucial for the establishment of cryptococcosis. In experimental cryptococcosis, the Th2 immune response is associated with host susceptibility, while Th1 cells are associated with protection. The absence of IL-27 receptor alpha in mice favor the increase Cryptococcus neoformans burden in the lung. Here, we evaluated the effects of the combination of IL-4, IFN-γ or IL-27 with C. gattii on human bronchial epithelial cells (BEAS-2B). METHODS: BEAS-2B were stimulated with IL-4, IFN-γ or IL-27 (100 ng/mL) and/or live yeast forms of C. gattii (multiplicities of infection (MOI) of 1-100) and vice-versa, as well as with heat-killed cells of C. gattii for 24 h. RESULTS: None of the C. gattii MOIs had cytotoxic effects on BEAS-2B when compared to control. The cells stimulated by cytokines (IL-4, IFN-γ or IL-27) followed by live yeast forms of C. gattii (MOI of 100) infection and vice-versa demonstrated a reduction in IL-6, IL-8 and/or CCL2 production and activation of STAT6 (induced by IL-4) and STAT1 (induced by IL-27 or IFN-γ) when compared to cells stimulated with C. gattii, IL-4, IFN-γ or IL-27. In the combination of cytokines and heat-killed cells of C. gattii, no inhibition of these inflammatory parameters was observed. The growth of C. gattii was increased while the phagocytosis of live yeast forms of C. gattii in the BEAS-2B were reduced in the presence of IL-4, IFN-γ or IL-27. Conclusion The association of live yeast forms, but not heat-killed yeast forms, of C. gattii with IL-4, IFN-γ or IL-27 induced an anti-inflammatory effect.

Compartment Syndrome Secondary to Bothrops spp. Envenomation in Triângulo Mineiro, Region, Minas Gerais, Brazil

ABSTRACT Background: Snakebite is a neglected global health problem with high morbidity. We describe compartment syndrome (CS) cases related to snakebites by Bothrops spp. Methods: The medical records of patients admitted with snakebites envenomation were reviewed. Results: Of 47 patients with Bothrops spp. envenomation (4 male; mean age: 42 years), 7 (15%) developed CS. The mean time to antivenom administration was 9.5 hours. The time to fasciotomy was variable. Seven patients developed infection and four had acute kidney injury. Conclusions: The incidence of CS is higher than that reported previously. This may be due to the clinical severity and long delay before administering antivenom.

Cryptococcus neoformans in Association with Dermatophagoides pteronyssinus has Pro- (IL-6/STAT3 Overproduction) and Anti-inflammatory (CCL2/ERK1/2 Downregulation) Effects on Human Bronchial Epithelial Cells.

Cryptococcosis (caused, for example, by Cryptococcus neoformans) and allergic asthma (caused, for example, by Dermatophagoides pteronyssinus) target the respiratory tract (the lung and bronchial epithelium). C. neoformans and D. pteronyssinus can coexist in the same indoor environment, and exposure to both can cause alterations in the local airway inflammatory milieu and exacerbation of airway inflammatory diseases. Here, we evaluated the effects of the association between C. neoformans and D. pteronyssinus in the modulation of airway inflammatory responses in an in vitro experimental model using human bronchial epithelial cells. BEAS-2B cells were cultivated and stimulated with D. pteronyssinus (10 µg/mL) and/or C. neoformans (MOI 100) for 24 h. No cytotoxic effect was observed in cells stimulated by C. neoformans and/or D. pteronyssinus. The production of IL-8, IL-6, and/or CCL2, but not IL-10, as well as the activation of NF-kB, STAT3, STAT6, and/or ERK1/2 were increased in cells stimulated by C. neoformans or D. pteronyssinus compared to controls. C. neoformans in association with D. pteronyssinus inhibited the CCL2­ERK1/2 signaling pathway in cells treated with both pathogens compared to cells stimulated by D. pteronyssinus alone. In addition, their association induced an additive effect on the IL-6/STAT3 signaling pathway in cells compared to cells stimulated with D. pteronyssinus or C. neoformans only. D. pteronyssinus increased the internalization and growth of C. neoformans in BEAS-2B cells. D. pteronyssinus in association with C. neoformans promoted pro- and anti-inflammatory responses, which can modulate cryptococcal infection and asthmaticus status.

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

ABSTRACT: 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 36(6): 1738-1748, 2022-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), V̇o2peak, 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.

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

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

Anti-inflammatory actions of aspirin-triggered resolvin D1 (AT-RvD1) in bronchial epithelial cells infected with Cryptococcus neoformans.

BACKGROUND: The interaction of Cryptococcus neoformans with airway epithelial cells is crucial for the establishment of cryptococcosis. Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways. METHOD: Here, we evaluated the effects of AT-RvD1 (1, 10 or 100 nM) on human bronchial epithelial cells (BEAS-2B) stimulated with C. neoformans (1, 10 or 100 multiplicities of infection; MOI). RESULTS: After 24 h, C. neoformans (all MOI) demonstrated no cytotoxic effects and increased IL-8 production on BEAS-2B cells when compared to controls. In addition, C. neoformans (MOI 100) increased the concentration of IL-6, but not of IL-10. AT-RvD1 (100 nM) significantly reduced the concentration of IL-8 and IL-6 and increased IL-10 production in C. neoformans-stimulated BEAS-2B cells. C. neoformans increased the phosphorylation of NF-κB and ERK1/2, and ALX/FPR2 expression. AT-RvD1 reduced the activation of NF-kB without altering the ERK1/2 and ALX/FPR2 expression. The anti-inflammatory effects of AT-RvD1 were dependent on the ALX/FPR2, once its antagonist (BOC2) reversed its anti-inflammatory effects. No alteration on the fungal burden as well as interactions with BEAS-2B cells was observed by AT-RvD1. CONCLUSION: AT-RvD1 demonstrated significant anti-inflammatory effects in bronchial epithelial cells infected with C. neoformans without affecting the development of C. neoformans infection in the airways. TRIAL REGISTRATION: Not applicable.

Effects of cigarette smoke extract on bronchial epithelial cells stimulated with Cryptococcus neoformans.

In the airways, the adhesion of Cryptococcus neoformans with airway epithelial cells is crucial for the establishment of cryptococcosis. Tobacco smoke is considered a risk factor for cryptococcosis. Here, we evaluated the effects of cigarette smoke extract (CSE) on human bronchial epithelial cells (BEAS-2B) stimulated with C. neoformans. Multiplicities of infection (MOIs) of 1-100 of C. neoformans per cell led to increased IL-8 production and no cytotoxic effects when compared to those of controls. C. neoformans (MOI 100) also significantly increased the concentration of IL-6. In cells stimulated with CSE doses (1.0, 2.5 and 5.0%) from one or five cigarettes, increased IL-1ß production was observed only in doses from one (1.0%) and five (2.5%) cigarettes when compared to that of controls. However, only 1.0% CSE failed to show cytotoxic effects. In addition, CSE significantly increased the concentration of IL-8. Cells stimulated with both CSE and C. neoformans demonstrated a reduction in IL-6/STAT3 signalling compared to that in cells stimulated by C. neoformans. In addition, a significant increase in IL-10 production was also observed. No alterations in NF-kB or ICAM-1 expression were observed among the groups. The combination of CSE and C. neoformans favoured the increase of fungal numbers and extracellular adhering of C. neoformans on BEAS-2B cells. In addition, the internalization of C. neoformans on BEAS-2B cells was reduced after CSE stimulation. In conclusion, the association of CSE and C. neoformans induced an anti-inflammatory effect in bronchial epithelial cells, which might favour the development of C. neoformans infection in the airways.

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

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

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.

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

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

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.

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

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.

Subclinical Carotid Atherosclerosis and Reduced DAD Score for Cardiovascular Risk Stratification in HIV-Positive Patients / Aterosclerose Carotídea Subclínica e DAD Escore Reduzido para Estratificação de Risco Cardiovascular em Pacientes HIV Positivos

Abstract 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.

Resumo Fundamento: Pacientes HIV positivos possuem 2 vezes maior risco que a população geral de apresentarem infarto e 4 vezes maior de morte súbita. Além do risco aumentado, esses indivíduos apresentam eventos cardiovasculares, em média, aproximadamente, 10 anos antes que a população geral. Objetivo: Comparar os escores Framingham e DAD reduzido para avaliação de risco cardiovascular em pacientes HIV positivos e o potencial impacto na decisão clínica após avaliação de aterosclerose carotídea subclínica. Métodos: Foram avaliados clinicamente 71 pacientes HIV positivos sem antecedentes de doenças cardiovasculares, estratificados pelos escores Framingham 2008 e DAD reduzido e submetidos a avaliação de aterosclerose carotídea subclínica. A concordância entre os escores foi avaliada pelo índice Kappa e os valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: A idade média foi 47,2 e 53,5% do sexo masculino. A ocorrência de aterosclerose subclínica foi de 39,4%. A concordância entre os escores foi de 49% com Kappa de 0,735 nos pacientes de alto risco. Não houve diferença significativa entre os escores por meio de análise de discriminação com curva ROC. Dos pacientes com risco intermediário no Framingham e DAD reduzido, 62,5% e 30,8% respectivamente apresentavam aterosclerose carotídea. Conclusão: O presente estudo mostrou correlação entre os escores e espessamento médio-intimal e alta concordância entre os pacientes classificados como alto risco nos escores Framingham 2008 e DAD escore reduzido. A observação de alta prevalência de aterosclerose carotídea em pacientes de risco intermediário sugere que grande parte desses pacientes poderia ser reclassificada como alto risco.

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

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.

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

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)-1ß 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-1ß, 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.

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

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.