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S. pneumoniae, commonly known as pneumococcus, is a naturally competent Gram-positive bacterium and is the major cause of pneumonia in elderly and children in developing countries. This pathogen is associated with respiratory diseases affected by pollution. The objective of this work was determining the effect of ash and environmental dust from the burning of sugarcane on pneumococci bacterial transformation. The transformation capacity of the Pn360 pneumococci strain was performed using the assays of DNA donor of mutant for luxS gene. Thus, the transformation tests were performed in contact with dust collected in the southwestern region of Brazil (important region where burning of sugar cane is present in the agriculture). The use of degradative practices in the sugar cane agriculture in Brazil was involved in the transformation capacity of the S. pneumoniae. This phenomenon includes important consequences for public health concerning to resistance acquisition and new virulence factors of this important infection. In conclusion, we obtained important results concerning the action of environmental pollution in Streptococcus pneumoniae transformation, increasing the DNA acquisition for this pathogen.
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Brazilian Purpuric Fever (BPF) is a hemorrhagic pediatric illness caused by Haemophilus influenzae biogroup aegyptius (Hae), a bacterium that was formerly associated with self-limited purulent conjunctivitis. BPF is assumed to be eradicated. However, the virulence mechanisms inherent to Hae strains associated with BPF is still a mystery and deficient in studies. Here, we aim to analyze the role of the autotransporter genes related to adherence and colonization las, tabA1, and hadA genes through RT-qPCR expression profiling and knockout mutants. Relative quantification by real-time PCR after infection in human cells and infant rat model suggests that las was initially downregulated probably duo to immune evasion, tabA1, and hadA were overexpressed in general, suggesting an active role of TabA1 and HadA1 adhesins in Hae in vitro and in vivo. Transformation attempts were unsuccessful despite the use of multiple technical approaches and in silico analysis revealed that Hae lacks genes related to competence in Haemophilus, which could be part of the elucidation of the difficulty of genetically manipulating Hae strains.
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OBJECTIVES: To assess the risks of and factors associated with mortality, loss to follow-up, and changing regimens after children with HIV infected perinatally initiate combination antiretroviral therapy (cART) in Latin America and the Caribbean. STUDY DESIGN: This 1997-2013 retrospective cohort study included 1174 antiretroviral therapy-naïve, perinatally infected children who started cART age when they were younger than 18 years of age (median 4.7 years; IQR 1.7-8.8) at 1 of 6 cohorts from Argentina, Brazil, Haiti, and Honduras, within the Caribbean, Central and South America Network for HIV Epidemiology. Median follow-up was 5.6 years (IQR 2.3-9.3). Study outcomes were all-cause mortality, loss to follow-up, and major changes in cART. We used Cox proportional hazards models stratified by site to examine the association between predictors and times to death or changing regimens. RESULTS: Only 52% started cART at younger than 5 years of age; 19% began a protease inhibitor. At cART initiation, median CD4 count was 472 cells/mm3 (IQR 201-902); median CD4% was 16% (IQR 10-23). Probability of death was high in the first year of cART: 0.06 (95% CI 0.04-0.07). Five years after cART initiation, the cumulative mortality incidence was 0.12 (95% CI 0.10-0.14). Cumulative incidences for loss to follow-up and regimen change after 5 years were 0.16 (95% 0.14-0.18) and 0.30 (95% 0.26-0.34), respectively. Younger children had the greatest risk of mortality, whereas older children had the greatest risk of being lost to follow-up or changing regimens. CONCLUSIONS: Innovative clinical and community approaches are needed for quality improvement in the pediatric care of HIV in the Americas.
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Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Causas de Morte , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Adolescente , Fármacos Anti-HIV/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Intervalos de Confiança , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Incidência , América Latina , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
This study explored the experiences of the first generation of adolescents who acquired HIV through vertical transmission when disclosing their diagnosis to friends and romantic partners. The study sample was selected by convenience, with 20 patients (13-20 years old) participating in a qualitative investigation using individual interviews (language: Portuguese; duration: 45â minutes). The participants were followed in specialized clinics for the treatment of pediatric AIDS in São Paulo, Brazil. The results suggest that families who live with HIV tend to keep it a secret, and such behavior is learned and accepted unquestioningly as natural. Respect for privacy and the fear of rejection, coupled with the belief that information about their disease will be spread, are the main beliefs with which participants justify their secrecy. In terms of romantic relationships, adolescents were aware that their HIV status should at some point be shared with current or future sexual partners. However, the decision to reveal an HIV diagnosis in romantic relationships is permeated by anxieties, uncertainties about the right time, and fear of abandonment. In any case, telling the truth requires trust, guarantees of the other's love, and, in some cases, probing romantic partners beforehand to learn their perceptions about the disease. Participants who had experiences disclosing their HIV status shared positive and negative results, including emotional support, acceptance, and understanding, along with ostracism, discrimination, and abandonment by family members. The findings of this paper reinforce the challenges of revealing an HIV diagnosis to third parties. It requires understanding the meaning and importance of the secret for each patient, along with the conflict between the right to confidentiality and the responsibility of treating others exposed to the disease. All these aspects should be discussed extensively with this population and incorporated into clinical practice.
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Comportamento do Adolescente , Infecções por HIV/psicologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Autorrevelação , Parceiros Sexuais/psicologia , Adolescente , Brasil , Feminino , Infecções por HIV/economia , Infecções por HIV/prevenção & controle , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: This study aimed to identify the prevalence of renal abnormalities and the evolution of glomerular filtration rate (GFR) among human immunodeficiency virus (HIV)- infected children and adolescents followed up in an infectious disease outpatient pediatric clinic. METHODS: We performed a cohort study of 115 children and adolescents. Outcomes of two evaluations for urinalysis, microalbuminuria/urinary creatinine ratio, urinary retinol-binding protein (uRBP) concentration, and estimated GFR (eGFR) were obtained for each patient, with an average interval of 6 months between evaluations. These changes were correlated with gender, age, race, body mass index (BMI), height-for-age (H/A) percentile, clinical and immunological classification of HIV infection, use of antiretroviral therapy (ART), HIV viral load (VL), and CD4+ T-lymphocyte count. RESULTS: Mean patient age at the time of inclusion in the study was 12.6 ± 3.2 years; 50.4 % were male, 81.7 % had acquired immune defeciency syndrome (AIDS), 80.9 % had CD4+ < 500 cells/mm(3), and 87.8 % were on ART. Urinary changes included hematuria (11.3 %), proteinuria (7 %), and microalbuminuria (11.6 %); uRBP was present in 3.8 %; and mean eGFR was 163 ± 32 ml/min/1.73 m(2). CONCLUSIONS: The subclinical renal abnormalities found in this study may indicate early manifestations of a broad spectrum of renal dysfunction associated with HIV and involves the decision to initiate or modify ART.
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Albuminúria/epidemiologia , Infecções por HIV/epidemiologia , Nefropatias/epidemiologia , Adolescente , Fatores Etários , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Instituições de Assistência Ambulatorial , Doenças Assintomáticas , Brasil/epidemiologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Inquéritos Epidemiológicos , Humanos , Lactente , Rim/fisiopatologia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Urinálise , Adulto JovemRESUMO
BACKGROUND: The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. METHODS: Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. RESULTS: A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups). CONCLUSIONS: In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.).
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Antirretrovirais/uso terapêutico , Infecções por HIV/prevenção & controle , HIV-1 , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Lamivudina/uso terapêutico , Nelfinavir/uso terapêutico , Nevirapina/uso terapêutico , Zidovudina/uso terapêutico , Antirretrovirais/efeitos adversos , Farmacorresistência Viral , Quimioterapia Combinada/efeitos adversos , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/transmissão , Humanos , Fórmulas Infantis , Recém-Nascido , Estimativa de Kaplan-Meier , Lamivudina/efeitos adversos , Masculino , Nelfinavir/efeitos adversos , Nevirapina/efeitos adversos , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez , Zidovudina/efeitos adversosRESUMO
Neglected agricultural products (NAPs) are defined as discarded material in agricultural production. Corn cobs are a major waste of agriculture maize. Here, a methanolic extract from corn cobs (MEC) was obtained. MEC contains phenolic compounds, protein, carbohydrates (1.4:0.001:0.001). We evaluated the in vitro and in vivo antioxidant potential of MEC. Furthermore, its antiproliferative property against tumor cells was assessed through MTT assays and proteins related to apoptosis in tumor cells were examined by western blot. MEC showed no hydroxyl radical scavenger capacity, but it showed antioxidant activity in Total Antioxidant Capacity and DPPH scavenger ability assays. MEC showed higher Reducing Power than ascorbic acid and exhibited high Superoxide Scavenging activity. In tumor cell culture, MEC increased catalase, metallothionein and superoxide dismutase expression in accordance with the antioxidant tests. In vivo antioxidant test, MEC restored SOD and CAT, decreased malondialdehyde activities and showed high Trolox Equivalent Antioxidant Capacity in animals treated with CCl4. Furthermore, MEC decreased HeLa cells viability by apoptosis due an increase of Bax/Bcl-2 ratio, caspase 3 active. Protein kinase C expression increased was also detected in treated tumor cells. Thus, our findings pointed out the biotechnological potential of corn cobs as a source of molecules with pharmacological activity.
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Antineoplásicos Fitogênicos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Extratos Vegetais/farmacologia , Zea mays/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose , Catalase/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Células HeLa , Humanos , Concentração Inibidora 50 , Metalotioneína/metabolismo , Metanol/química , Oxirredução , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Extração em Fase Sólida , Solventes/química , Superóxido Dismutase/metabolismo , Superóxidos/químicaRESUMO
The WHO recommends the integration of routine HIV services within maternal and child health (MCH) services to reduce the fragmentation of and to promote retention in care for pregnant and postpartum women living with HIV (WWH) and their infants and children exposed to HIV (ICEH). During 2020-2021, we surveyed 202 HIV treatment sites across 40 low- and middle-income countries within the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We determined the proportion of sites providing HIV services integrated within MCH clinics, defined as full [HIV care and antiretroviral treatment (ART) initiation in MCH clinic], partial (HIV care or ART initiation in MCH clinic), or no integration. Among sites serving pregnant WWH, 54% were fully and 21% partially integrated, with the highest proportions of fully integrated sites in Southern Africa (80%) and East Africa (76%) compared to 14%-40% in other regions (i.e., Asia-Pacific; the Caribbean, Central and South America Network for HIV Epidemiology; Central Africa; West Africa). Among sites serving postpartum WWH, 51% were fully and 10% partially integrated, with a similar regional integration pattern to sites serving pregnant WWH. Among sites serving ICEH, 56% were fully and 9% were partially integrated, with the highest proportions of fully integrated sites in East Africa (76%), West Africa (58%) and Southern Africa (54%) compared to ≤33% in the other regions. Integration was heterogenous across IeDEA regions and most prevalent in East and Southern Africa. More research is needed to understand this heterogeneity and the impacts of integration on MCH outcomes globally.
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Introduction: Routine patient care data are increasingly used for biomedical research, but such "secondary use" data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.
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MC3T3-E1 cells grown in the presence of ascorbic acid and ß-glycerophosphate (AA/ß-GP) express alkaline phosphatase and produce an extensive collagenous extracellular matrix. Differentiated MC3T3-E1 cells are more sensitive to hydrogen peroxide-induced oxidative stress than undifferentiated cells. In this study, we compared the profile of antioxidant enzymes and molecular markers of apoptosis in undifferentiated and differentiated MC3T3-E1 cells (cell differentiation was induced by treatment with AA/ß-GP). Differentiated osteoblasts showed lower expression and activity of catalase, glutathione S-transferase and glutathione peroxidase. The total superoxide dismutase activity and the expression of Cu/Zn superoxide dismutase were also lower, while the expression of Mn superoxide dismutase was higher in differentiated osteoblasts. The level of malondialdehyde, a widely used marker for oxidative stress, was lower in the AA/ß-GP group compared with control cells, but this difference was not significant. Western blotting showed that treatment with AA/ß-GP increased the Bax/Bcl-2 ratio used as an index of cellular vulnerability to apoptosis. In addition, the activities of caspases 3, 8 and 9 and cleaved poly (ADP) ribose polymerase were significantly higher in differentiated cells. These findings provide new insights into how changes in the activities of major antioxidant enzymes and in the signaling pathways associated with apoptosis may influence the susceptibility of bone cells to oxidative stress.
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Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Diferenciação Celular/efeitos dos fármacos , Glicerofosfatos/farmacologia , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Animais , Western Blotting , Linhagem Celular , Peróxido de Hidrogênio/farmacologia , CamundongosRESUMO
The goal of this study was to evaluate changes in plasma human immunodeficiency virus (HIV) RNA concentration [viral load (VL)] and CD4+ percentage (CD4%) during 6-12 weeks postpartum (PP) among HIV-infected women and to assess differences according to the reason for receipt of antiretrovirals (ARVs) during pregnancy [prophylaxis (PR) vs. treatment (TR)]. Data from a prospective cohort of HIV-infected pregnant women (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. Women experiencing their first pregnancy who received ARVs for PR (started during pregnancy, stopped PP) or for TR (initiated prior to pregnancy and/or continued PP) were included and were followed PP. Increases in plasma VL (> 0.5 log10) and decreases in CD4% (> 20% relative decrease in CD4%) between hospital discharge (HD) and PP were assessed. Of the 1,229 women enrolled, 1,119 met the inclusion criteria (PR: 601; TR: 518). At enrollment, 87% were asymptomatic. The median CD4% values were: HD [34% (PR); 25% (TR)] and PP [29% (PR); 24% (TR)]. The VL increases were 60% (PR) and 19% (TR) (p < 0.0001). The CD4% decreases were 36% (PR) and 18% (TR) (p < 0.0001). Women receiving PR were more likely to exhibit an increase in VL [adjusted odds ratio (AOR) 7.7 (95% CI: 5.5-10.9) and a CD4% decrease (AOR 2.3; 95% CI: 1.6-3.2). Women receiving PR are more likely to have VL increases and CD4% decreases compared to those receiving TR. The clinical implications of these VL and CD4% changes remain to be explored.
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Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Infecções por HIV/virologia , Complicações Infecciosas na Gravidez/virologia , Carga Viral , Adulto , Região do Caribe , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , América Latina , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos , RNA ViralRESUMO
The aim of this study was to characterize the urinary excretion of the BK (BKV) and JC (JCV) human polyomaviruses in a cohort of human immunodeficiency virus (HIV)-infected children and adolescents. One hundred and fifty-six patients were enrolled: Group I included 116 HIV-infected children and adolescents [median age = 11.4 years (y); range 1-22 y]; Group II included 40 non-HIV-infected healthy controls (median age = 11.37 y; range 7-16 y). Single urine samples from both groups were screened for the presence of JCV and BKV DNA by polymerase chain reaction at enrolment. The overall rate of JCV and BKV urinary excretion was found to be 24.4% and 40.4%, respectively (n = 156). Group I had urinary excretion of JCV and BKV in 27.6% and 54.3% of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5% of subjects and for BKV in 12.5% of subjects (p Pearson JCV = 0.20; p Pearson BKV < 0.0001). In Group I, there was no association between JCV/BKV shedding and age, gender or CD4 values. Patients with an HIV viral load < 50 copies/mL had a lower excretion of BKV (p < 0.001) and a trend of lower JCV excretion (p = 0.07). One patient in Group I (1/116, 0.9%) showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.
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Infecções Oportunistas Relacionadas com a AIDS/virologia , Vírus BK/isolamento & purificação , Vírus JC/isolamento & purificação , Infecções por Polyomavirus/urina , Infecções Tumorais por Vírus/urina , Infecções Oportunistas Relacionadas com a AIDS/urina , Adolescente , Vírus BK/genética , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , DNA Viral/urina , Feminino , Humanos , Lactente , Vírus JC/genética , Masculino , Reação em Cadeia da Polimerase , Carga Viral , Adulto JovemRESUMO
INTRODUCTION: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. METHODS: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. RESULTS: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p = 0.022, Fisher's exact test). CONCLUSION: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.
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Infecções por HIV , Cirrose Hepática , Adolescente , Adulto , Aspartato Aminotransferases , Biomarcadores , Brasil , Criança , Estudos Transversais , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Adulto JovemRESUMO
BACKGROUND: Little is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology. METHODS: Children (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models. RESULTS: A total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation -0.001; 95% CI -0.18 to 0.17). CONCLUSIONS: Poor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1 , Adolescente , Fármacos Anti-HIV/administração & dosagem , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Haiti/epidemiologia , Honduras/epidemiologia , Humanos , Masculino , Resultado do Tratamento , Carga ViralRESUMO
Lymphocyte subsets, activation markers and apoptosis were assessed in 20 HIV-exposed noninfected (ENI) children born to HIV-infected women who were or not exposed to antiretroviral (ARV) drugs during pregnancy and early infancy. ENI children and adolescents were aged 6-18 years and they were compared to 25 age-matched healthy non-HIV-exposed children and adolescents (Control). ENI individuals presented lower CD4(+) T cells/mm(3) than Control group (control: 1120.3 vs. ENI: 876.3; t-test, p = 0.030). ENI individuals had higher B-cell apoptosis than Control group (Control: 36.6%, ARV exposed: 82.3%, ARV nonexposed: 68.5%; Kruskal-Wallis, p < 0.05), but no statistical difference was noticed between those exposed and not exposed to ARV. Immune activation in CD4(+) T, CD8(+) T and in B cells was comparable in ENI and in Control children and adolescents. Subtle long-term immune alterations might persist among ENI individuals, but the clinical consequences if any are unknown, and these children require continued monitoring.
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Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , Infecções por HIV/transmissão , HIV-1/imunologia , Transmissão Vertical de Doenças Infecciosas , Adolescente , Antirretrovirais/uso terapêutico , Apoptose/fisiologia , Linfócitos B/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , Estudos de Casos e Controles , Criança , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Ativação Linfocitária/imunologia , Masculino , Gravidez/imunologia , Carga ViralRESUMO
Chronic meningococcemia is a rare manifestation of meningococcal disease, characterized by a period of more than one week of intermittent or continuous fever, arthralgia and skin lesions without meningitis. It can occur both in previously healthy and immunocompromised patients. The gold standard for the diagnosis is culture isolation of Neisseria meningitidis in sterile material. We describe a case of a vertically HIV-infected adolescent with chronic meningococcal disease.
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BACKGROUND: HIV infection and juvenile systemic lupus erythematosus (jSLE) are risk factors for the development of herpes zoster (HZ) and its complications. Both diseases share similar immunologic aspects, such as immunodeficiency and immune activation. Therefore, our objective was to evaluate and compare the frequency and characteristics of HZ episodes in pediatric patients with HIV infection and jSLE. METHODS: A retrospective cohort study was carried out with the evaluation of 2 pediatric cohorts: HIV patients who were followed from January 1987 to December 2014 and patients with jSLE followed up from January 1990 to December 2014 in outpatient clinics. RESULTS: Of the 190 HIV patients, 48 had HZ (25.3%), with 67 episodes; of the 92 patients with jSLE, 27 had HZ (29.3%), totaling 28 episodes. The median age at the first episode of HZ was higher in the jSLE than in the HIV group (8.9 vs. 12.5 years, respectively) (P = 0.020). HIV patients were more likely to have recurrent HZ (P = 0.025). In addition, there was a tendency for HIV patients to present with disseminated HZ more frequently (P = 0.060). Although the hospitalization rate was similar between groups, patients with jSLE received intravenous acyclovir more frequently (P = 0.014). When HIV non-immune reconstitution syndrome patients were compared with jSLE group, recurrence of HZ in HIV was the only significant difference between groups (P = 0.017). CONCLUSIONS: Patients with HIV had more recurrent HZ than patients with jSLE.
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Infecções por HIV/complicações , Herpes Zoster/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Adolescente , Criança , Pré-Escolar , Feminino , Infecções por HIV/virologia , Humanos , Lactente , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
The guided tissue regeneration (GTR) technique can be applied in dentistry and other medical specializations, such as orthopedics. In modern dentistry, GTR has been used in periodontics and implantology to treat periodontal defects, to reconstruct lost, damaged and atrophied bone tissue in dental implant procedures, and to preserve alveolar bases after tooth extraction. In order to create and improve new therapies and to develop new biomaterials that restore, improve and prevent aggravation of compromised tissue function, poly (ϵ-caprolactone) (PCL) polymer membranes were obtained by the electrospinning process and were associated with two plant extracts: Pterodon pubescens Benth (P. pubescens) and Arrabidaea chica Verlot (A. chica) which are characterized by their pharmacological activities of anti-inflammatory and healing actions, respectively. Fiber morphology was analyzed using scanning electron microscopy (SEM), where fiber average diameter was measured from SEM images. Contact angle measurements were performed in order to evaluate the hydrophilicity of electrospun membranes containing vegetal extract. High-performance liquid chromatography was used to evaluate the ability to release active ingredients. Cytotoxicity and cell proliferation assays were performed in vitro on NIH-3T3 cells for 1, 3 and 7 d. Electrospun PCL membranes associated with plant extracts P. pubescens and/or A. chica presented a controlled release profile of the active compounds induced fibroblast formation, suggesting that they are promising and suitable for applications in GTR.
Assuntos
Fibroblastos/metabolismo , Regeneração Tecidual Guiada/métodos , Poliésteres/química , Animais , Anti-Inflamatórios/farmacologia , Materiais Biocompatíveis/química , Regeneração Óssea/efeitos dos fármacos , Proliferação de Células , Eletroquímica , Técnicas In Vitro , Camundongos , Microscopia Eletrônica de Varredura , Células NIH 3T3 , Nanofibras/química , Extratos Vegetais , Engenharia Tecidual , Alicerces Teciduais , Cicatrização/efeitos dos fármacosRESUMO
INTRODUCTION: As integrase inhibitors become available in low- and middle-income countries (LMICs), they offer the potential to expand extremely limited treatment options available to children and adolescents. In LMICs, only small numbers have used raltegravir, primarily as part of third-line regimens. Using data from the IeDEA global consortium, we aimed to describe the characteristics of children on raltegravir-containing regimens and their outcomes. METHODS: We included data from 1994 to 2017 from children (age <18 years), from East and Southern Africa, Asia and South America, who received cART regimens containing raltegravir for ≥90 days. We describe their characteristics at raltegravir start, and their immunological and virological outcomes. RESULTS AND DISCUSSION: In total, 62 children were included, with median age at raltegravir initiation of 14.3 years (IQR 11.2 to 15.8) and median CD4 count of 276 cells/µL (IQR 68 to 494). Among 40 (65%) with drug resistance testing prior to raltegravir, 71% were resistant to at least one protease inhibitor (PI), and 32% had high-level resistance to at least one drug class. Most (n = 50; 81%) received raltegravir as part of third-line cART following PI-based regimens, and were on regimens containing four or more drugs (n = 47, 76%). By database closure, median duration on raltegravir was 2.0 years (IQR 0.8 to 3.0), 1 (1.6%) patient had died, 6 (9.7%) were lost to follow-up and 21 (34%) had discontinued raltegravir. Among 15 patients reporting reasons for stopping raltegravir, six discontinued because it was no longer available. Within one year of starting raltegravir, among 53 patients with VL measures, 40 (75%) had VL < 1000 copies/mL, and among 54 with a reported CD4 count, 45 (83%) and 36 (67%) were ≥350 and ≥500 cells/µL, respectively, with median CD4 count increasing to 517.5 cells/µL (IQR 288 to 810). CONCLUSIONS: Among children in LMICs, the initial use of raltegravir has been primarily for post PI-based cART. We found good virological and immunological outcomes despite frequent prior triple-class failure and high levels of drug resistance. Both access to raltegravir and long-term adherence to regimens with large pill-burdens remain challenging. Policies which promote earlier access to new drugs and simplify daily regimens for children and adolescents in LMICs are needed.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Raltegravir Potássico/uso terapêutico , Adolescente , África Austral , Ásia , Contagem de Linfócito CD4 , Criança , Feminino , Infecções por HIV/economia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Pobreza , América do Sul , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
INTRODUCTION: Audits play a critical role in maintaining the integrity of observational cohort data. While previous work has validated the audit process, sending trained auditors to sites ("travel-audits") can be costly. We investigate the efficacy of training sites to conduct "self-audits." METHODS: In 2017, eight research groups in the Caribbean, Central, and South America network for HIV Epidemiology each audited a subset of their patient records randomly selected by the data coordinating center at Vanderbilt. Designated investigators at each site compared abstracted research data to the original clinical source documents and captured audit findings electronically. Additionally, two Vanderbilt investigators performed on-site travel-audits at three randomly selected sites (one adult and two pediatric) in late summer 2017. RESULTS: Self- and travel-auditors, respectively, reported that 93% and 92% of 8919 data entries, captured across 28 unique clinical variables on 65 patients, were entered correctly. Across all entries, 8409 (94%) received the same assessment from self- and travel-auditors (7988 correct and 421 incorrect). Of 421 entries mutually assessed as "incorrect," 304 (82%) were corrected by both self- and travel-auditors and 250 of these (72%) received the same corrections. Reason for changing antiretroviral therapy (ART) regimen, ART end date, viral load value, CD4%, and HIV diagnosis date had the most mismatched corrections. CONCLUSIONS: With similar overall error rates, findings suggest that data audits conducted by trained local investigators could provide an alternative to on-site audits by external auditors to ensure continued data quality. However, discrepancies observed between corrections illustrate challenges in determining correct values even with audits.