Assuntos
Dengue , Complicações Infecciosas na Gravidez , Feminino , Humanos , Gravidez , Protocolos Clínicos , Dengue/diagnóstico , Dengue/prevenção & controle , Dengue/terapia , Período Pós-Parto , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/terapia , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/terapia , Transtornos Puerperais/prevenção & controleAssuntos
Humanos , Feminino , Gravidez , Dengue/diagnóstico , Dengue/prevenção & controle , Dengue/terapia , Período Pós-PartoRESUMO
Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection. Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry. 53 women were HPV+ against 127 women HPV-. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries. In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Antígenos HLA-G/genética , Neoplasias do Colo do Útero/genética , Displasia do Colo do Útero/genética , Inflamação , Fatores de Transcrição Forkhead/genética , Papillomaviridae/genéticaRESUMO
Introduction: Syphilis is an infectious systemic disease caused by the bacterium Treponema pallidum. The Amaury de Medeiros Integrated University Health Center in Recife is a reference maternity hospital for high-risk pregnancies and the management of the most common Sexually Transmitted Infections during prenatal care, including Gestational Syphilis and Congenital Syphilis. Objective: To determine the epidemiological profile of the population exposed to these conditions, the rate of Gestational Syphilis detection, the incidence of Congenital Syphilis, and the associated unfavorable outcomes in Amaury de Medeiros Integrated University Health Center between January 2019 and December 2021. Methods: This retrospective cohort study included pregnant women and neonates diagnosed with syphilis at Amaury de Medeiros Integrated University Health Center. Data were collected from the Notification/Investigation Forms for Gestational Syphilis and Congenital Syphilis, between January 2019 and December 2021. Results: At Amaury de Medeiros Integrated University Health Center, 463 cases of Gestational Syphilis and 296 of Congenital Syphilis were reported. During the three-year study, 4444, 4360, and 4265 live births were recorded, confirming the Gestational Syphilis detection rates 33.30, 36.92, and 36.10 per 1000 live births, with the incidence of Congenital Syphilis being 26.1, 21.33, and 20.39 per 1000 live births. Pregnant women in their third trimester who were brown, had incomplete primary education, and lived in an urban area were the main sociodemographic variables. In total, 217 (73.3%) patients were diagnosed with Gestational Syphilis during or after delivery, indicating a low prenatal coverage (70.6%). In terms of the progression of Congenital Syphilis, unfavorable outcomes was found in 40 (13.5%) patients, including 16 (40%) abortions, 10 (25%) stillbirths, nine (22.5%) deaths from Congenital Syphilis, and 5 (12.5%) deaths from other causes. Conclusion: Gestational Syphilis detection rates and Congenital Syphilis incidence remain alarming, with abortions and stillbirths being the most common unfavorable outcomes. To change the dramatic situation of Congenital Syphilis in Brazil, the associated factors point to a poor quality of prenatal care and an urgent need to change public policies for pregnant women and newborns, in conjunction with socioeconomic assistance
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Complicações Infecciosas na Gravidez/epidemiologia , Sífilis Congênita/epidemiologia , Brasil/epidemiologia , Sífilis/diagnóstico , Sífilis/transmissão , Sífilis/epidemiologia , Incidência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1, and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions.
Assuntos
Neoplasias , Infecções por Papillomavirus , Humanos , Feminino , Apresentação de Antígeno , Papillomavirus Humano , Infecções por Papillomavirus/genética , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Membrana Transportadoras/genética , Polimorfismo de Nucleotídeo Único , Peptídeos/genéticaRESUMO
OBJECTIVE: High-grade cervical lesions (HSIL) are associated with the presence of high-risk HPV types, tissue expression of p16, and increased chance of malignant progression, requiring surgical intervention. To improve risk evaluation, we assessed the discriminatory power of the histological findings associated with p16 immunohistochemistry (IHC) staining to classify the low-grade cervical lesion (LSIL) and HSIL. METHODS: We collected cervical biopsies from colposcopy-visible lesions and non-affected tissue (adjacent to the lesions) of 62 Brazilian women and labeled them with anti-p16 antibodies. In addition to the observational pattern and labeling to define the latent classes (affected vs. non-affected), a computational tool was used for semi-quantitative analysis of p16 expression. The intensity of staining of the nucleus or cytoplasm was captured using the Gimp 2.10 software. ROC curves were used to determine cutoff values for p16 expression in patients classified as LSIL and HSIL by latent class statistics for each labeling stratum. RESULTS: p16 nuclear labeling showed the best sensitivity and specificity to discriminate LSIL with low p16 expression (62%) and HSIL with high p16 expression (37%). Many patients whose lesions had intermediate levels of p16 nuclear staining were subsequently stratified according to the expression of p16 in the cytoplasm, indicating that five of 21 LSIL were at risk of progression, and 13 of 41 HSIL at risk of regression. CONCLUSIONS: We suggest a hierarchical analysis, with histology at the first level, followed by a labeling analysis in the nucleus and then in the cytoplasm to increase the accuracy of the HPV cervical lesion stratification.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/análise , Medição de Risco , Displasia do Colo do Útero , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Brasil , Colo do Útero/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Esfregaço Vaginal , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologiaRESUMO
The high-risk oncogenic human papillomavirus (HPV) has developed mechanisms for evasion of the immune system, favoring the persistence of the infection. The chronic inflammation further contributes to the progression of tissue injury to cervical cancer. The programmed cell death protein (PD-1) after contacting with its ligands (PD-L1 and PD-L2) exerts an inhibitory effect on the cellular immune response, maintaining the balance between activation, tolerance, and immune cell-dependent lesion. We evaluated 295 patients exhibiting or not HPV infection, stratified according to the location (injured and adjacent non-injured areas) and severity of the lesion (benign, pre-malignant lesions). Additionally, we investigated the role of the promoter region PDCD1 -606G>A polymorphism (rs36084323) on the studied variables. PD-1 and PDCD1 expression were evaluated by immunohistochemistry and qPCR, respectively, and the PDCD1 polymorphism was evaluated by nucleotide sequencing. Irrespective of the severity of the lesion, PD-1 levels were increased compared to adjacent uninjured areas. Additionally, in cervical intraepithelial neoplasia (CIN) I, the presence of HPV was associated with increased (P = 0.0649), whereas in CIN III was associated with decreased (P = 0.0148) PD-1 levels, compared to the uninjured area in absence of HPV infection. The PDCD1 -606A allele was rare in our population (8.7%) and was not associated with the risk for development of HPV infection, cytological and histological features, and aneuploidy. In contrast, irrespective of the severity of the lesion, patients exhibiting the mutant PDCD1 -606A allele at single or double doses exhibited increased protein and gene expression when compared to the PDCD1 -606GG wild type genotype. Besides, the presence of HPV was associated with the decrease in PDCD1 expression and PD-1 levels in carriers of the -606 A allele presenting severe lesions, suggesting that other mediators induced during the HPV infection progression may play an additional role. This study showed that increased PD-1 levels are influenced by the -606G>A nucleotide variation, particularly in low-grade lesions, in which the A allele favors increased PDCD1 expression, contributing to HPV immune system evasion, and in the high-grade lesion, by decreasing tissue PD-1 levels.
Assuntos
Infecções por Papillomavirus , Receptor de Morte Celular Programada 1 , Displasia do Colo do Útero , Alelos , Apoptose , Feminino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Receptor de Morte Celular Programada 1/genética , Displasia do Colo do Útero/genéticaRESUMO
The topics of congenital syphilis and children exposed to syphilis compose the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Such document was elaborated based on scientific evidence and validated in discussions with specialists. This article provides guidelines for syphilis in pregnant women and congenital syphilis clinical management, emphasizing the vertical transmission of Treponema pallidum prevention. Epidemiological and clinical aspects of these infections are presented and recommendations for managers in the programmatic and operational management of syphilis. The article also includes guidelines for health professionals in screening, diagnosing, and treating people with sexually transmitted infections and their sex partners, in addition to strategies for surveillance actions, prevention, and control of the disease. Most congenital syphilis cases arise from test failures in prenatal care or inadequate or no treatment of maternal syphilis.
Assuntos
Complicações Infecciosas na Gravidez , Infecções Sexualmente Transmissíveis , Sífilis Congênita , Sífilis , Brasil/epidemiologia , Criança , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/prevenção & controle , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/prevenção & controle , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sífilis/epidemiologia , Sífilis Congênita/diagnóstico , Sífilis Congênita/prevenção & controleRESUMO
This article addresses sexual violence, as part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health. Guidance is provided in programmatic and operational management, focusing on the service network for people in situation of sexual violence, recommendations to health staff about pregnancy and viral and non-viral sexually transmitted infections prophylactic measures, in addition to surveillance action strategies. Sexual violence is an encompassing issue that includes wider areas than the health field. It involves conceptual and programmatic challenges for health staff, at the forefront of care for affected people and also to the implementation of prevention strategies addressed to the whole society. Sexual violence is one of the principal forms of human rights violation, affecting the right to life, health, and bodily integrity.