RESUMO
Human T-limphotropic virus 1 infection has a global distribution, with a high prevalence in some regions of Brazil and the world, while HTLV-2 infection is endemic mainly among indigenous people and drug users. To analyze intrafamilial transmission of HTLV-1/2 in five Kayapó indigenous peoples (Gorotire, Kararaô, Kokraimoro, Kubenkokre, and Xikrin do Bacajá), we investigated 1452 individuals who underwent serological and molecular tests. Among the 276 indigenous people with positive results, we identified intrafamily transmission in 42.7% of cases, representing 38 families. It was possible to suggest horizontal and vertical transmissions in 15.8% (6/38) and 47.4% (18/38) of the family groups, respectively. In 15.8%, it was not possible to suggest the route, which indicated that the transmission may have occurred through both vertical and horizontal routes. Through phylogenetic analyses, 35 samples positive for HTLV-2 were sequenced and classified as subtype 2c, and the two samples that tested positive for HTLV-1 were shown to belong to the cosmopolitan subtype, transcontinental subgroup (HTLV-1aA). This study confirms the intrafamilial transmission of HTLV-1/2 infection in indigenous people of the Brazilian Amazon, highlighting the importance of the sexual and mother-to-child transmission routes in maintaining the virus in these people.
Assuntos
Infecções por HTLV-I , Infecções por HTLV-II , Vírus Linfotrópico T Tipo 1 Humano , Vírus Linfotrópico T Tipo 2 Humano , Povos Indígenas , Filogenia , Humanos , Brasil/epidemiologia , Infecções por HTLV-I/transmissão , Infecções por HTLV-I/virologia , Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/classificação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/classificação , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Feminino , Masculino , Infecções por HTLV-II/transmissão , Infecções por HTLV-II/virologia , Infecções por HTLV-II/epidemiologia , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Criança , Transmissão Vertical de Doenças Infecciosas , Pré-Escolar , Prevalência , IdosoRESUMO
This study aimed to describe the prevalence of HTLV-1/2 in quilombola communities in the state of Pará and investigate the possible sociodemographic risk factors associated with the infection, as well as to trace the occurrence of the familial transmission of the virus. A total of 310 individuals living in eight quilombos located in the state of Pará (northern Brazil) were investigated for the presence of anti-HTLV-1/2 antibodies using an enzyme-linked immunosorbent assay (ELISA), and positive samples were confirmed using Western blot and/or real-time quantitative polymerase chain reaction (qPCR). Participants answered a questionnaire about sociodemographic aspects and risk factors for infection. Anti-HTLV-1/2 antibodies were detected in two individuals (one man and one woman), for an overall seroprevalence of 0.65%. Both individuals belonged to the community of São José de Icatú. The search for intrafamilial infection identified two other infected women, which increased the general prevalence of HTLV-1 among the Icatú to 6.25% (4/64). Western blot and qPCR confirmed their HTLV-1 infection, and phylogenetic analysis demonstrated that the isolates were of the cosmopolitan subtype and transcontinental subgroup. Epidemiological investigation of the cases revealed that the three women, at some point in their lives, had a relationship with the infected male individual. HTLV-1 is transmitted silently between individuals in the community of São José de Icatú with a present or past family relationship, stressing the need for screening and laboratory diagnosis to prevent further dissemination of the virus and surveillance of disease emergence.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Filogenia , Humanos , Brasil/epidemiologia , Feminino , Masculino , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/transmissão , Infecções por HTLV-I/virologia , Adulto , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 1 Humano/classificação , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Adulto Jovem , Fatores de Risco , Prevalência , Adolescente , População Negra , Idoso , Vírus Linfotrópico T Tipo 2 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/imunologiaRESUMO
Some genetic variations in cytokine genes can alter their expression and influence the evolution of Mycobacterium tuberculosis (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the IFNG +874A/T, IL6 -174G/C, IL4 -590C/T, and IL10 -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA (IFNG +874A/T), GG (IL6 -174G/C), TT (IL4 -590C/T), and GG (IL10 -1082A/G) were associated with an increased risk of TB compared to that of LTBI (p = 0.0027; p = 0.0557; p = 0.0286; p = 0.0361, respectively) and the control (p = <0.0001, p = 0.0021; p = 0.01655; p = 0.0132, respectively). In combination, the A allele for IFNG +874A/T and the T allele for IL4 -590C/T were associated with a higher chance of TB (p = 0.0080; OR = 2.753 and p < 0.0001; OR = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated (p < 0.05). The genotype and wild-type allele for IFNG +874A/T and the genotype and polymorphic allele for IL4 -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.
Assuntos
Tuberculose Latente , Tuberculose , Humanos , Citocinas/genética , Tuberculose Latente/genética , Interleucina-10/genética , Interleucina-6/genética , Brasil , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Predisposição Genética para DoençaRESUMO
Human T lymphotropic virus 1 (HTLV-1) is a retrovirus associated with inflammatory diseases, including HTLV-1-associated myelopathy (HAM), and host genetic factors may be involved in disease evolution. The forkhead Box P3 (FOXP3) transcription factor is linked to homeostasis of the immune system, and the presence of polymorphisms in the promoter region of the FOXP3 gene should reflect its expression levels and consequent activation of regulatory T cells, which may contribute to severe inflammatory disorders, such as HAM. This study evaluated the rs2232365 polymorphism (-924 A/G) located in the promoter region of the FOXP3 gene and its association with HAM. Forty DNA samples from asymptomatic carriers and 25 samples from HAM patients were used, in addition to 130 control samples. The polymorphism was genotyped by conducting real-time polymerase chain reaction (PCR) (quantitative PCR [qPCR]) on extracted DNA. The proviral loads (PVLs) and CD4+ and CD8+ T lymphocyte counts were determined by qPCR and FACSCalibur flow cytometry, respectively. The PVLs, CD4+ T lymphocyte concentrations, and tumor necrosis factor-α dosages were considered predictive factors of the clinical profiles of HTLV-1 infection, all of which had higher levels in the HAM group. Carriers of the GG genotype for the polymorphism rs2232365 had high PVLs and CD4+ T lymphocyte concentrations.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Paraparesia Espástica Tropical/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Polimorfismo de Nucleotídeo Único , Infecções por HTLV-I/genética , Fatores de Transcrição Forkhead/genética , Carga Viral , Provírus/genética , Provírus/metabolismoRESUMO
TNF-α is a Th1 cytokine profile active in the control of Mycobacterium tuberculosis infection, IL-10 is associated with persistence of bacterial infection. The aim of the study was to investigate the association of TNFA -308G/A and IL10 -819C/T polymorphisms and TNFA and IL10 gene expression levels with pulmonary and extrapulmonary tuberculosis (n = 200) and control (n = 200). The individuals were submitted to genotyping and quantification of gene expression performed by real-time quantitative polymerase chain reaction (qPCR). No association was observed between the frequencies of polymorphisms evaluated and pulmonary tuberculosis. The frequency of polymorphic genotypes for TNFA -308G/A were associated with the extrapulmonary tuberculosis (p = 0.0445). The levels of TNFA expression were lower in the pulmonary tuberculosis group than in the control (p = 0.0009). There was a positive correlation between the levels of TNFA and IL10 in patients with pulmonary tuberculosis (r = 0.560; p = 0.0103). Reduced levels of TNFA expression may promote the formation of an anti-inflammatory microenvironment, favoring the persistence of the bacillus in the host, contributing to the establishment of pulmonary tuberculosis.
Assuntos
Interleucina-10 , Tuberculose Pulmonar , Humanos , Interleucina-10/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Brasil , Genótipo , Fator de Necrose Tumoral alfa/genética , Expressão Gênica , Frequência do GeneRESUMO
Genetic variations in components of the immune response seem to be an important factor that contributes to the manifestation of symptoms of some diseases related to HTLV-1 infection. Nerve growth factor (NGF) and the p75 neurotrophin receptor (p75NTR) are related to the maintenance of neurons and the activation of the immune response. In this study, we evaluated the association of the NGF -198C/T, NGF Ala35Val, and p75NTR Ser205Leu polymorphisms with HTLV-1 infection and plasma cytokine levels in 166 samples from individuals infected with HTLV-1 (59 symptomatic and 107 asymptomatic). The genotyping and quantification of the proviral load were performed by real-time PCR, and cytokine levels were measured by ELISA. The NGF -198C/T and NGF Ala35Val polymorphisms were not associated with HTLV-1 infection. The frequency of the Ser/Leu genotype of p75NTR Ser205Leu was more frequent in the control group (p = 0.0385), and the Ser/Leu genotype and allele Leu were more frequent among the asymptomatic (p < 0.05), especially with respect to the HTLV-1-associated myelopathy (HAM) group (p < 0.05). The symptomatic showed a higher proviral load and higher TNF-α and IL-10 levels (p < 0.05). Asymptomatic carriers of the Ser/Leu genotype (p = 0.0797) had lower levels of proviral load and higher levels of TNF-α (p = 0.0507). Based on the results obtained, we conclude that the p75NTR Ser205Leu polymorphism may be associated with reduced susceptibility to HTLV-1 infection, a lower risk of developing symptoms, including HAM, and better infection control.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Citocinas , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Fator de Crescimento Neural , Provírus/genética , Receptor de Fator de Crescimento Neural , Fator de Necrose Tumoral alfa , Carga ViralRESUMO
A multi-epitope protein expressed in a prokaryotic system, including epitopes of Env, Gag, and Tax proteins of both HTLV-1 and HTLV-2 was characterized for HTLV-1/2 serological screening. This tool can contribute to support the implementation of public policies to reduce HTLV-1/2 transmission in Brazil, the country with the highest absolute numbers of HTLV-1/2 infected individuals. The chimeric protein was tested in EIA using serum/plasma of HTLV-infected individuals and non-infected ones from four Brazilian states, including the North and Northeast regions (that present high prevalence of HTLV-1/2) and Southeast region (that presents intermediate prevalence rates) depicting different epidemiological context of HTLV-1/2 infection in our country. We enrolled samples from Pará (n = 114), Maranhão (n = 153), Minas Gerais (n = 225) and São Paulo (n = 59) states; they are from blood donors' candidates (Pará and Minas Gerais), pregnant women (Maranhão) and HIV+/high risk for sexually transmitted infection (STI; São Paulo). Among the HTLV-1/2 positive sera, there were co-infections with viral (HTLV-1 + HTLV-2, HIV, HCV, and HBV), bacterial (Treponema pallidum) and parasitic (Trypanosoma cruzi, Schistosma mansoni, Strongyloides stercoralis, Entamoeba coli, E. histolytica, and Endolimax nana) pathogens related to HTLV-1/2 co-morbidities that can contribute to inconclusive diagnostic results. Sera positive for HIV were included among the HTLV-1/2 negative samples. Considering both HTLV-1 and HTLV-2-infected samples from all states and different groups (blood donor candidates, pregnant women, and individuals with high risk for STI), mono or co-infected and HTLV-/HIV+, the test specificity ranged from 90.09 to 95.19% and the sensitivity from 82.41 to 92.36% with high accuracy (ROC AUC = 0.9552). This multi-epitope protein showed great potential to be used in serological screening of HTLV-1 and HTLV-2 in different platforms, even taking into account the great regional variation and different profile of HTLV-1 and HTLV-2 mono or co-infected individuals.
Assuntos
Infecções por HIV , Infecções por HTLV-I , Infecções por HTLV-II , Vírus Linfotrópico T Tipo 1 Humano , Infecções Sexualmente Transmissíveis , Brasil/epidemiologia , Epitopos , Feminino , Infecções por HIV/diagnóstico , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/diagnóstico , Infecções por HTLV-II/epidemiologia , Vírus Linfotrópico T Tipo 2 Humano , Humanos , Gravidez , Infecções Sexualmente Transmissíveis/epidemiologiaRESUMO
Human T-lymphotropic virus 1 (HTLV-1) is endemic worldwide and the infection results in severe diseases, including Adult T-cell Leukemia (ATL) and HTLV-1 associated myelopathy (HAM). There are some limitations of employing the present commercial serological assays for both diagnostic and epidemiological purposes in different geographical areas of the Brazil, such as the Amazon Region. Currently, methods for diagnosis are usually expensive to adapt for routine use. The aim of this work was to identify and characterize specific ligands to IgG that mimic HTLV-1 epitopes through the Phage Display technique, which could be used for diagnosis and as future vaccine candidates. Initially, IgG from 10 patients with HTLV-1 and 20 negative controls were covalently coupled to protein G-magnetic beads. After biopanning, genetic sequencing, bioinformatics analysis and Phage-ELISA were performed. The technique allowed the identification of 4 clones with HTLV-1 mimetic peptides, three aligned with gp46, A6 (SPYW), B6 (SQLP) and D7 (PLIL), and one with the protease and Tax, A8 (SPPR). Clones A6 and B6 showed higher values of accessibility, antigenicity and hydrophilicity. The reactivity of the clones evaluated by the Receiver Operating Characteristic (ROC) curve showed that the B6 clone had the highest Area Under Curve (0.83) and sensitivity and specificity values (both were 77.27 %; p < 0.001). The study showed that the Phage Display technique is effective for the identification of HTLV-1-related peptides. Clone B6 indicated to be a good marker for bioprospecting diagnostic test for HTLV-1 infection and could be used as a possible vaccine candidate for future studies.
RESUMO
The dysregulation of cytokine production can lead to an inefficient immune response, promoting viral persistence that induces the progression of chronic viral hepatitis. The study investigated the association of the IL6-174G/C polymorphism with changes in cytokine levels and its influence on the persistence and progression of chronic hepatitis caused by HBV and HCV in 72 patients with chronic hepatitis B (HBV), 100 patients with hepatitis C (HCV), and a control group of 300 individuals. The genotyping of the IL6-174G/C polymorphism was performed by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). HCV patients with the wild-type genotype (GG) had a higher viral load (p = 0.0230). The plasma levels of IL-6 were higher among patients infected with HBV and HCV than among the control group (p < 0.0001). Patients with HCV were associated with increased inflammatory activity (A2−A3; p < 0.0001). In hepatitis C, carriers of the GG genotype had higher levels of IL-6 (p = 0.0286), which were associated with A2−A3 inflammatory activity (p = 0.0097). Patients with A2−A3 inflammatory activity and GG genotype had higher levels of IL-6 than those with the GC/CC genotype (p = 0.0127). In conclusion, the wild-type genotype for the IL6-174G/C polymorphism was associated with high levels of IL-6 and HCV viral load and inflammatory activity, suggesting that this genotype may be a contributing factor to virus-induced chronic infection.
Assuntos
Hepatite C Crônica , Hepatite C , Brasil/epidemiologia , Citocinas/genética , Genótipo , Hepacivirus/genética , Vírus da Hepatite B , Hepatite C Crônica/genética , Humanos , Interleucina-6/genéticaRESUMO
Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is an important immune mechanism against infection. This study investigated the association of tuberculosis (TB) with the presence of the polymorphisms FAS -670A/G and FASL -124A/G, the levels of sFas and sFasL, and the gene expression of FASL and cytokines. Samples of 200 individuals diagnosed with TB and 200 healthy controls were evaluated. Real-time PCR (genotyping and gene expression) and ELISA (dosages of sFas, sFasL, IFN-γ, and IL-10) tests were performed. There was no association of FAS -670A/G and FASL -124A/G polymorphisms with TB. The TB group exhibited high plasma levels of sFas and reduced plasma levels of sFasL (p < 0.05). The correlation analysis between these markers revealed a positive correlation between the levels of sFas and sFasL, sFasL and FASL expression, and between sFas and FASL expression (p < 0.05). In the TB group, there was a positive correlation between FASL expression and IFN-γ levels and higher levels of IL-10 compared to IFN-γ (p < 0.05). High levels of sFas and reduced levels of sFasL and FASL expression may contribute to the inhibition of apoptosis in infected cells and represent a possible bacterial resistance resource to maintain the infection.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Interleucina-10/genética , Proteína Ligante Fas/genética , Ensaio de Imunoadsorção Enzimática , Tuberculose/genética , Expressão GênicaRESUMO
HTLV-1/2 infection is endemic in Indigenous peoples of the Americas. Its origin is attributed to the migratory flow of Amerindian ancestral peoples. The present study aimed to investigate the seroprevalence of HTLV-1/2 infection in Indigenous peoples of the Brazilian Amazon. A total of 3350 Indigenous people belonging to 15 communities were investigated. The investigation was performed using serological (ELISA), molecular (qPCR) and confirmatory (Western blot and/or Inno-Lia) tests to detect and differentiate the infection. The seroprevalence was 8.3% for HTLV-1/2 infection, with 0.1% of individuals seropositive for HTLV-1 and 8.1% for HTLV-2. The prevalence of infection was statistically higher in women (10.1%) than in men (6.5%) (p = 0.0002). This female predominance was observed in all age groups; in females the prevalence was significant from 41 years old (p < 0.0001) and in males from 51 years old (p < 0.0001). Here, we present a prevalence of HTLV-1/2 among Indigenous peoples of the Brazilian Amazon. The endemic infection in these groups must reflect the different epidemiological profiles observed in these peoples, such as sexual transmission through rejection of condom use, breastfeeding, especially in cases of cross-breastfeeding, and the high rate of pregnancy in the villages.
Assuntos
Infecções por HTLV-I , Infecções por HTLV-II , Vírus Linfotrópico T Tipo 1 Humano , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Vírus Linfotrópico T Tipo 2 Humano , Vírus Linfotrópico T Tipo 1 Humano/genética , Brasil/epidemiologia , Estudos Soroepidemiológicos , Infecções por HTLV-II/epidemiologia , Infecções por HTLV-I/epidemiologia , Povos IndígenasRESUMO
BACKGROUND: Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA -308G>A and IL10 -1082A>G polymorphisms in the susceptibility and progress of chronic hepatitis C. METHOD: The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. RESULTS: The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and its absence could be associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. CONCLUSION: Our results suggest the polymorphic genotype at TNFA -308G>A as protective against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A>G variant associated with higher HCV viral load. Further studies must be performed in order to confirm these associations.
Assuntos
Hepacivirus , Hepatite C Crônica , Biomarcadores , Genótipo , Hepatite C Crônica/genética , Humanos , Interleucina-10/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfaRESUMO
Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.
Assuntos
Infecções por HTLV-I/transmissão , Infecções por HTLV-II/transmissão , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Vírus Linfotrópico T Tipo 2 Humano/fisiologia , Brasil/epidemiologia , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Infecções por HTLV-II/epidemiologia , Infecções por HTLV-II/virologia , Política de Saúde , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/genética , Humanos , Política PúblicaRESUMO
Infection by human T-cell lymphotropic virus type 1 (HTLV-1) occurs in lymphocytes, which travel throughout the body, thus affecting several target organs and causing varied clinical outcomes, particularly in populations that are underserved and do not have access to healthcare. However, the mechanism of pathogenesis is not yet fully understood. The TAX and HTLV-1 basic leucine zipper factor (HBZ) proteins maintain viral persistence and affect pathogenesis through cell proliferation and immune and inflammatory responses that accompany each clinical manifestation. TAX expression leads to inhibition of transcription error control, OX40 overexpression, and cell proliferation in adult T-cell leukemia (ATL). OX40 levels are elevated in the central nervous system (CNS), and the expression of TAX in the CNS causes neuronal damage and loss of immune reactivity among patients with HTLV-1-associated myelopathy (HAM). HBZ reduces viral replication and suppresses the immune response. Its cell compartmentalization has been associated with the pathogenesis of HAM (cytoplasmic localization) and ATL (nuclear localization). TAX and HBZ seem to act antagonistically in immune responses, affecting the pathogenesis of HTLV-1 infection. The progression from HTLV-1 infection to disease is a consequence of HTLV-1 replication in CD4+ T and CD8+ T lymphocytes and the imbalance between proinflammatory and anti-inflammatory cytokines. The compartmentalization of HBZ suggests that this protein may be an additional tool for assessing immune and inflammatory responses, in addition to those already recognized as potential biomarkers associated with progression from infection to disease (including human leukocyte antigen (HLA), killer immunoglobulin-like receptors (KIR), interleukin (IL)-6, IL-10, IL-28, Fas, Fas ligand, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and mannose-binding lectin).
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Fatores de Transcrição de Zíper de Leucina Básica , Biomarcadores , Humanos , Proteínas dos RetroviridaeRESUMO
An inefficient immune response against the hepatitis C virus (HCV), combined with viral evasion mechanisms, is responsible for the chronicity of infection. The need to evaluate the innate mechanisms of the immune response, such as TLR3 and IFN-λ3, and their relationship with the virus-host interaction is important for understanding the pathogenesis of chronic hepatitis C. The present study aimed to investigate the gene expressions of TRL3 and IFNL3 in liver tissue, seeking to evaluate whether these could be potential biomarkers of HCV infection. A total of 23 liver biopsy samples were collected from patients with chronic HCV, and 8 biopsies were collected from healthy control patients. RNA extraction, reverse transcription and qPCR were performed to quantify the relative gene expressions of TLR3 and IFNL3. Data on the viral load; AST, ALT, GGT and AFP levels; and the viral genotype were collected from the patients' medical records. The intrahepatic expression of TLR3 (p = 0.0326) was higher in chronic HCV carriers than in the control group, and the expression of IFNL3 (p = 0.0037) was lower in chronic HCV carriers than in the healthy control group. The expression levels of TLR3 (p = 0.0030) and IFNL3 (p = 0.0036) were higher in the early stages of fibrosis and of necroinflammatory activity in the liver; in contrast, TLR3 and IFNL3 expressions were lower in the more advanced stages of fibrosis and inflammation. There was no correlation between the gene expression and the serum viral load. Regarding the initial METAVIR scale scores, liver transaminase levels were lower in patients with advanced fibrosis when correlated with TLR3 and IFNL3 gene expressions. The results suggest that in the early stages of the development of hepatic fibrosis, TLR3 and IFN-λ3 play important roles in the antiviral response and in the modulation of the tolerogenic liver environment because there is a decrease in the intrahepatic expressions of TLR3 and IFNL3 in the advanced stages of fibrosis, probably due to viral evasion mechanisms.
Assuntos
Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Interferons/genética , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Receptor 3 Toll-Like/genética , Biomarcadores , Biópsia , Estudos Transversais , Suscetibilidade a Doenças , Expressão Gênica , Perfilação da Expressão Gênica , Genoma Viral , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferons/metabolismo , Masculino , Índice de Gravidade de Doença , Receptor 3 Toll-Like/metabolismo , Carga ViralRESUMO
INTRODUCTION: We present a data analysis and review of recent studies regarding the laboratory diagnosis of human T-lymphotropic virus 1 and 2 (HTLV-1/2) infections in Brazil. METHODS: Target populations, available diagnostic serological assays (screening and complementary tests), molecular assays (in-house), causes of false-positive and false-negative results, and flowcharts were analyzed. RESULTS: A table presents the target populations, two diagnostic flowcharts (depending on laboratory infrastructure and study population), and recent research that may improve how HTLV-1/2 is diagnosed in Brazil. CONCLUSIONS: Our results support the implementation of public policies to reduce HTLV-1/2 transmission and its associated diseases.
Assuntos
Infecções por HTLV-I , Infecções por HTLV-II , Vírus Linfotrópico T Tipo 1 Humano , Brasil , Técnicas de Laboratório Clínico , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-II/diagnóstico , Infecções por HTLV-II/epidemiologia , Vírus Linfotrópico T Tipo 2 Humano , Humanos , Design de SoftwareRESUMO
Sexually transmitted infections (STIs) represent a worldwide public health problem and, although many of them are curable, they continue to be neglected, especially in areas with a low human development index, such as in the northern region of Brazil. This review describes the results of 30 years of studies at the Virus Laboratory at the Federal University of Pará, including the prevalence and molecular epidemiology of HIV-1, HTLV-1/2, HPV, HBV, Treponema pallidum and Chlamydia trachomatis among urban and non-urban populations, and also in vulnerable groups in the Brazilian Amazon. Control strategies and challenges in preventing STIs are discussed considering this immense geographic region, where essential health services are unable to reach the entire population, especially the most vulnerable, such as female sex workers, people who use illicit drugs, remnants of quilombolos and indigenous communities.
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Monitoramento Epidemiológico , Saúde Pública , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Populações Vulneráveis/estatística & dados numéricos , Brasil/epidemiologia , Infecções por Chlamydia/epidemiologia , Infecções por HIV/epidemiologia , Soropositividade para HIV , Prevalência , Profissionais do Sexo/estatística & dados numéricos , Comportamento Sexual , Infecções Sexualmente Transmissíveis/parasitologia , Infecções Sexualmente Transmissíveis/virologiaRESUMO
Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. Several studies have shown a higher prevalence of HPV infection in HIV-infected women. The aim of this study was to determine the prevalence and the genotype diversity of HPV infection in HIV-infected women. From April 2010 to December 2012 cervical specimens were collected from 169 HIV-infected women who screening for cervical cancer at Reference Unit in Belém. The detection of HPV infection was performed by nested PCR and HPV type was performed using a commercial system. The prevalence of HPV infection was 63.3%. Of the 47 genotyped samples, 40.4% was found positive for high risk-HPV 16 and 12.8% for high risk-HPV 52. HPV infection was predominant in the group of women with no incidence of cytological abnormalities and more prevalent in women of reproductive age, unmarried, low education level, and who reported use condoms during sexual intercourse. It was observed an association between HPV infection and independent variables, such as condom use, multiple sexual partners, and history of sexually transmitted diseases. High-risk types of HPV infection were prevalent in our study. Infection with multiple high-risk HPV genotypes may potentiate the development of cervical cancer in HIV-infected women.
Assuntos
Infecções por HIV , Infecções por Papillomavirus , Brasil/epidemiologia , Estudos Transversais , DNA Viral , Feminino , Infecções por HIV/complicações , Humanos , Infecções por Papillomavirus/epidemiologia , Prevalência , Fatores de RiscoRESUMO
This article addresses the Human T-lymphotropic virus (HTLV). This subject comprises the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health. HTLV-1/2 infection is a public health problem globally, and Brazil has the largest number of individuals living with the virus. HTLV-1 causes several clinical manifestations of neoplasm (adult T-cell leukemia/lymphoma) and inflammatory nature, such as HTLV-1-associated myelopathy and other manifestations such as uveitis, arthritis, and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health authorities professionals regarding viral transmission, diagnosis, treatment, and monitoring of individuals living with HTLV-1 and 2 in Brazil. HTLV-1/2 transmission can occur through blood transfusion and derivatives, injectable drug use, organ transplantation, unprotected sexual intercourse, and vertical transmission.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Infecções Sexualmente Transmissíveis , Adulto , Brasil , Infecções por HTLV-I/diagnóstico , Humanos , Qualidade de Vida , Literatura de Revisão como Assunto , Linfócitos TRESUMO
This manuscript is related to the chapter about human T-cell lymphotropic virus (HTLV) that is part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Health Ministry. HTLV-1/2 infection is a worldwide public health problem and Brazil has the largest number of individuals living with the virus. HTLV-1 causes a variety of clinical manifestations of a neoplastic nature, such as adult leukemia/T-cell lymphoma, and also of an inflammatory nature, such as HTLV-1-associated myelopathy, as well as other manifestations such as uveitis, arthritis and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health service managers and workers regarding virus transmission modes, diagnosis, treatment and monitoring of individuals living with HTLV-1 and 2 in Brazil.
O artigo aborda a infecção pelo vírus linfotrópico de células T humanas (human T lymphotropic virus, HTLV), tema contemplado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil. A infecção pelo HTLV-1/2 é um problema de saúde pública mundial, sendo o Brasil o país a referir o maior número de indivíduos convivendo com o vírus. O HTLV-1 causa diversas manifestações clínicas, de natureza neoplásica, como a leucemia/linfoma de células T do adulto, e de natureza inflamatória, a exemplo da mielopatia associada ao HTLV-1 e outras alterações, como uveíte, artrite e dermatite infecciosa. Estas patologias apresentam elevada morbimortalidade e impactam negativamente a qualidade de vida dos indivíduos infectados. A presente revisão inclui informações relevantes para gestores e profissionais de saúde sobre os mecanismos de transmissão viral, diagnóstico, tratamento e acompanhamento de indivíduos vivendo com o HTLV-1/2 no Brasil.
El artículo está relacionado con el capítulo sobre virus linfotrópico de células T humanas (human T lymphotropic virus, HTLV) que conforma el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil. La infección por HTLV-1/2 es un problema de salud pública en el mundo y Brasil tiene el mayor número de personas que viven con el virus. El HTLV-1 causa varias manifestaciones clínicas, de naturaleza neoplásica (leucemia/linfoma de células T adultas), y de naturaleza inflamatoria, como la mielopatía asociada al HTLV-1 y otras manifestaciones como la uveítis, la artritis y la dermatitis infecciosa. Estas patologías tienen una alta morbilidad y mortalidad e impactan negativamente en la calidad de vida de las personas infectadas. Esta revisión incluye información relevante para gerentes y profesionales de la salud sobre los mecanismos de transmisión viral, diagnóstico, tratamiento y monitoreo de personas que viven con HTLV-1 y 2 en Brasil.