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1.
Curr Issues Mol Biol ; 45(9): 6958-6966, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37754223

RESUMO

Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to São Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology.

2.
PLoS One ; 18(8): e0291027, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37651462

RESUMO

BACKGROUND: Redondovirus (ReDoV) is a DNA virus present in the respiratory tract of many healthy individuals. Since SARS-CoV-2, the virus responsible for COVID-19, also primarily infects the same site, we evaluated whether ReDoV was present at increased frequency in patients with COVID-19 and influenced infection parameters. METHODS: Saliva samples were collected weekly from 59 individuals with COVID-19 and from 132 controls. ReDoV was detected by polymerase chain reaction and the genotypes were identified by metagenomics. Torque Teno Virus (TTV) in these samples were previously reported. RESULTS: ReDoV was detected in saliva more frequently from COVID-19 patients (72.9%) than from controls (50.0%) (p = 0.0015). There were no associations between ReDoV detection and either continuous or intermittent SARS-CoV-2 shedding, the duration of SARS-CoV-2 detection in saliva, patients' sex or if infection was by the B1 or Gamma strain. The two ReDoV strains, Brisavirus and Vientovirus, were present in equivalent frequencies in ReDoV-positive COVID-19 patients and controls. Phylogenetic analysis suggested that the two ReDoV strains in Brazil were similar to strains previously detected on other continents. CONCLUSION: ReDoV expression in saliva is increased in males and females in Brazil with mild COVID-19 but its presence does not appear to influence properties of the SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Feminino , Masculino , Humanos , Brasil/epidemiologia , Filogenia , Saliva
3.
PLoS One ; 17(1): e0262672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35051215

RESUMO

Torquetenovirus (TTV) is a nonpathogenic endogenous virus whose abundance varies with the extent of immune system activation. We determined if the TTV titer in the vagina of pregnant women was associated with vaginal microbiota composition and levels of compounds in vaginal secretions. Vaginal TTV and microbiota composition in 494 second trimester pregnant women were identified by gene amplification and analysis. Vaginal matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMP) and lactic acid isomers were measured by ELISA. Dominance was defined as the relative abundance of a specific bacterium or species at >50% of the total number of bacteria identified. Clinical data were obtained by chart review. The median log10 TTV titer was lowest when Lactobacillus species other than L. iners were dominant (<1.0) as compared to when L. iners (4.1, p = 0.0001), bacteria other than lactobacilli (4.5, p = 0.0016) or no bacterium (4.7, p = 0.0009) dominated. The TTV titer was inversely proportional to L. crispatus abundance (p<0.0001) and directly proportional to levels of G. vaginalis (p = 0.0008) and L. iners (p = 0.0010). The TTV titer was proportional to TIMP-1, TIMP-2, MMP-8 and MMP-9 abundance (p≤0.0002) and inversely proportional to the level of D-lactic acid (p = 0.0024). We conclude that the association between variations in the TTV titer and the relative abundance of specific bacterial species and vaginal compounds indicates that local changes in immune status likely influence vaginal fluid composition.


Assuntos
Microbiota/fisiologia , Torque teno virus/isolamento & purificação , Vagina/microbiologia , Adulto , Feminino , Humanos , Gravidez , Gestantes , Vagina/virologia
4.
PLoS One ; 16(8): e0256357, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34428230

RESUMO

Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.


Assuntos
Biomarcadores/análise , COVID-19/diagnóstico , Saliva/virologia , Torque teno virus/isolamento & purificação , Adulto , COVID-19/virologia , DNA Viral/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Reação em Cadeia da Polimerase , Prognóstico , SARS-CoV-2/isolamento & purificação , Torque teno virus/genética
5.
J Med Virol ; 93(9): 5603-5607, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33851749

RESUMO

It has been estimated that individuals with COVID-19 can shed replication-competent virus up to a maximum of 20 days after initiation of symptoms. The majority of studies that addressed this situation involved hospitalized individuals and those with severe disease. Studies to address the possible presence of SARS-CoV-2 during the different phases of COVID-19 disease in mildly infected individuals, and utilization of viral culture techniques to identify replication-competent viruses, have been limited. This report describes two patients with mild forms of the disease who shed replication-competent virus for 24 and 37 days, respectively, after symptom onset.


Assuntos
COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/crescimento & desenvolvimento , Cultura de Vírus , Animais , Chlorocebus aethiops , Feminino , Humanos , Pessoa de Meia-Idade , SARS-CoV-2/patogenicidade , Células Vero/ultraestrutura , Células Vero/virologia , Carga Viral , Eliminação de Partículas Virais
6.
BMJ Open ; 11(1): e042745, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436471

RESUMO

BACKGROUND: Despite most cases not requiring hospital care, there are limited community-based clinical data on COVID-19. METHODS: The Corona São Caetano programme is a primary care initiative providing care to all residents with COVID-19 in São Caetano do Sul, Brazil. It was designed to capture standardised clinical data on community COVID-19 cases. After triage of potentially severe cases, consecutive patients presenting to a multimedia screening platform between 13 April and 13 May 2020 were tested at home with SARS-CoV-2 reverse transcriptase (RT) PCR; positive patients were followed up for 14 days with phone calls every 2 days. RT-PCR-negative patients were offered additional SARS-CoV-2 serology testing to establish their infection status. We describe the clinical, virological and natural history features of this prospective population-based cohort. FINDINGS: Of 2073 suspected COVID-19 cases, 1583 (76.4%) were tested by RT-PCR, of whom 444 (28.0%, 95% CI 25.9 to 30.3) were positive; 604/1136 (53%) RT-PCR-negative patients underwent serology, of whom 52 (8.6%) tested SARS-CoV-2 seropositive. The most common symptoms of confirmed COVID-19 were cough, fatigue, myalgia and headache; whereas self-reported fever (OR 3.0, 95% CI 2.4 to 3.9), anosmia (OR 3.3, 95% CI 2.6 to 4.4) and ageusia (OR 2.9, 95% CI 2.3 to 3.8) were most strongly associated with a positive COVID-19 diagnosis by RT-PCR or serology. RT-PCR cycle thresholds were lower in men, older patients, those with fever and arthralgia and closer to symptom onset. The rates of hospitalisation and death among 444 RT-PCR-positive cases were 6.7% and 0.7%, respectively, with older age and obesity more frequent in the hospitalised group. CONCLUSION: COVID-19 presents in a similar way to other mild community-acquired respiratory diseases, but the presence of fever, anosmia and ageusia can assist the specific diagnosis. Most patients recovered without requiring hospitalisation with a low fatality rate compared with other hospital-based studies.


Assuntos
COVID-19/diagnóstico , COVID-19/fisiopatologia , Atenção Primária à Saúde/métodos , Adolescente , Adulto , Fatores Etários , Brasil , COVID-19/complicações , Criança , Estudos de Coortes , Tosse/etiologia , Tosse/fisiopatologia , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Febre/etiologia , Febre/fisiopatologia , Cefaleia/etiologia , Cefaleia/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , SARS-CoV-2 , Fatores Sexuais , Adulto Jovem
7.
Reprod Sci ; 27(11): 2075-2081, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32944879

RESUMO

Vaginal samples from women with term deliveries were tested for torquetenovirus (TTV) by gene amplification, matrix metalloproteinase (MMP)-8 and D- and L-lactic acid by ELISA, and microbiome composition by analysis of the bacterial 16S ribosomal RNA gene. TTV was detected in 43.2%, 31.5%, and 41.4% of first trimester, third trimester, and postpartum samples, respectively. The viral titer was higher in postpartum than in the first (p = 0.0018) or third (p = 0.0013) trimester. The mean gestational age at delivery was lower in women positive for TTV in their first trimester (p = 0.0358). In the first and third trimester, the MMP-8 level was higher if TTV was also present (p < 0.0091). The D-lactic acid level was lower in first trimester samples if TTV was present (p = 0.0334). Lactobacillus crispatus dominance in first and third trimester samples was higher when TTV was absent (p < 0.0033). We conclude that TTV is present in the vagina in many women with normal pregnancy outcomes and that its occurrence is associated with a lack of L. crispatus dominance, an increase in vaginal MMP-8 and a decrease in D-lactic acid.


Assuntos
Infecções por Vírus de DNA , Ácido Láctico/análise , Lactobacillus crispatus , Metaloproteinase 8 da Matriz/análise , Complicações na Gravidez/virologia , Torque teno virus , Vagina/virologia , Adulto , Líquidos Corporais/virologia , Feminino , Humanos , Lactobacillus crispatus/isolamento & purificação , Período Pós-Parto , Gravidez , Resultado da Gravidez , Trimestres da Gravidez , Torque teno virus/isolamento & purificação
8.
J Oral Microbiol ; 13(1): 1858002, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33391631

RESUMO

Background: SARS-CoV-2 quickly spreads in the worldwide population, imposing social restrictions to control the infection, being the massive testing another essential strategy to break the chain of transmission. Aim: To compare the performance of at-home self-collected samples - saliva and combined nasal-oropharyngeal swabs (NOP) - for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance. Material and methods: We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling was combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar® SARS-CoV-2 RT-PCR Kit 1.0.  Results: There was an overall significant agreement (κ coefficient value of 0.58) between saliva and NOP. Considering results in either sample, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva. Conclusion: Our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions.

9.
Braz J Infect Dis ; 23(1): 34-39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30849332

RESUMO

BACKGROUND: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. OBJECTIVES: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. METHODS: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. RESULTS: Two thousand patients were included; 55.1% were male, mean age 58±11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. CONCLUSIONS: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients.


Assuntos
Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Idoso , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Fatores Socioeconômicos , Fatores de Tempo
10.
Braz. j. infect. dis ; Braz. j. infect. dis;23(1): 34-39, Jan.-Feb. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001496

RESUMO

ABSTRACT Background: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. Objectives: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. Methods: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. Results: Two thousand patients were included; 55.1% were male, mean age 58 ± 11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. Conclusions: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Fatores Socioeconômicos , Fatores de Tempo , Brasil/epidemiologia , Estudos Transversais , Distribuição por Sexo
11.
Ann Hepatol ; 17(6): 959-968, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30600291

RESUMO

INTRODUCTION AND AIM: Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection. MATERIAL AND METHODS: All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12). RESULTS: The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event. DISCUSSION: The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).


Assuntos
Anilidas/administração & dosagem , Antivirais/administração & dosagem , Carbamatos/administração & dosagem , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Compostos Macrocíclicos/administração & dosagem , Ribavirina/administração & dosagem , Ritonavir/administração & dosagem , Sulfonamidas/administração & dosagem , Uracila/análogos & derivados , 2-Naftilamina , Adulto , Idoso , Anilidas/efeitos adversos , Antivirais/efeitos adversos , Brasil , Carbamatos/efeitos adversos , Ciclopropanos , Combinação de Medicamentos , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Lactamas Macrocíclicas , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Compostos Macrocíclicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , RNA Viral/sangue , RNA Viral/genética , Ribavirina/efeitos adversos , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/efeitos adversos , Valina , Carga Viral
12.
J Med Virol ; 89(12): 2249-2254, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28700085

RESUMO

Spontaneously occurring resistance may impair the success of protease inhibitors based regimens in HCV treatment. This study aimed to evaluate associations between amino acid substitutions in NS3/NS4A domain and clinical features of 247 HCV mono or HCV/HIV co-infected patients. Fourteen samples (5.7%) harbored at least one resistance-associated substitution (RAS). The following RASs were detected in NS3 region: T54S (6-2.4%), V55A (7-2.8%), and Q80R (2-0.8%). S122G occurred in 86.9% of HCV genotype 1b samples with either natural polymorphisms or RASs. Advanced liver fibrosis and HIV co-infection were not related to NS3/NS4A amino acid substitutions.


Assuntos
Coinfecção , Infecções por HIV/complicações , Hepacivirus/genética , Hepatite C Crônica/virologia , Polimorfismo Genético , Proteínas não Estruturais Virais/genética , Adulto , Antivirais/uso terapêutico , Brasil/epidemiologia , Farmacorresistência Viral/genética , Feminino , Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepacivirus/enzimologia , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Inibidores de Proteases/uso terapêutico , Análise de Sequência de DNA
14.
Antivir Ther ; 21(8): 653-660, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27314166

RESUMO

BACKGROUND: As a result of increased understanding of the HCV life cycle, a new generation of drugs known as direct-acting antivirals (DAAs) was developed and is constantly being improved. At baseline, HCV variants resistant to DAA therapy may pre-exist, increasing the likelihood of treatment failure. The aim of this study was to investigate the presence of resistance-associated variants (RAVs) in treatment-naive patients infected with HCV subtypes 1a and 1b. METHODS: Next-generation sequencing was used to assess the frequencies of NS3-4A, NS5A and NS5B RAVs in 100 HCV monoinfected DAA-naive patients (HCV-1a: n=51; HCV-1b: n=49). RESULTS: Complete HCV sequence information was obtained for most samples. RAVs were detected in the NS3-4A (T54S, V55A, Q80K and R155K), NS5A (Q30H/R, H58P and Y93C/H/N) and NS5B (A421V) regions in 10%, 22% and 8%, respectively, of patients infected with HCV subtype-1a. Among the patients infected with HCV subtype-1b, mutations in the NS3-4A (F43I, T54S, Q80H, D168E and M175L), NS5A (L28M, R30Q, L31M, Q54H, A92T and Y93H) and NS5B (L159F, C316N, A421V and S556G) regions were observed in 12%, 53% and 31% of patients, respectively. CONCLUSIONS: High-throughput DNA sequencing allows an easier and more complete analysis of DAA RAVs, including mutations that represent only a minor variant of the whole viral population. RAVs to the three different classes of DAAs were found in our population. The characterization of their profile in the circulating virus is relevant to determine the better treatment option for infected individuals or to guide the implementation of treatment policies.


Assuntos
Farmacorresistência Viral/genética , Hepacivirus/genética , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Proteínas não Estruturais Virais/genética , Adulto , Antivirais/farmacologia , Feminino , Hepacivirus/classificação , Hepacivirus/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade
15.
Antivir Ther ; 20(4): 387-95, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25624410

RESUMO

BACKGROUND: Nucleoside/nucleotide analogue (NA) treatment causes selection pressure for HBV strains carrying mutations conferring NA resistance. Drug-resistance mutations occur in the reverse transcriptase (RT) region of the HBV polymerase gene and spontaneously arise during viral replication. These mutations can also alter the hepatitis B surface (HBs) protein and in some cases reduce binding to HBs antibodies. The spread of NA-resistant HBV may impact the efficacy of antiviral treatment and hepatitis B immunization programmes. In this study, we used direct sequencing to assess the occurrence of HBV carrying known mutations that confer NA resistance in the largest cohort of treatment-naive patients with chronic hepatitis B (CHB) to date. METHODS: HBV DNA samples isolated from 702 patients were sequenced and the RT region subjected to mutational analysis. RESULTS: There was high genetic variability among the HBV samples analysed: A1 (63.7%), D3 (14.5%), A2 (3.3%), A3 (0.1%), B1 (0.1%), B2 (0.1%), C2 (0.9%), D1 (0.9%), D2 (4.6%), D4 (5.1%), D unclassified subgenotype (0.7%), E (0.6%), F2a (4.6%), F4 (0.4%) and G (0.4%). HBV strains harbouring mutations conferring NA resistance alone or combined with compensatory mutations were identified in 1.6% (11/702) of the patients. CONCLUSIONS: HBV strains harbouring resistance mutations can comprise the major population of HBV quasispecies in treatment-naive patients. In Brazil, there is a very low frequency of untreated patients who are infected with these strains. These findings suggest that the spread and natural selection of drug-resistant HBV is an uncommon event and/or most of these strains remain unstable in the absence of NA selective pressure.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral/genética , Produtos do Gene pol/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Mutação , Adenina/análogos & derivados , Adenina/farmacologia , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Brasil , DNA Viral/genética , DNA Viral/imunologia , Produtos do Gene pol/antagonistas & inibidores , Produtos do Gene pol/metabolismo , Genótipo , Guanina/análogos & derivados , Guanina/farmacologia , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/imunologia , Humanos , Lamivudina/farmacologia , Testes de Sensibilidade Microbiana , Organofosfonatos/farmacologia , Estudos Retrospectivos , Análise de Sequência de DNA , Tenofovir/farmacologia , Replicação Viral/efeitos dos fármacos
16.
Antivir Ther ; 20(3): 281-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25279715

RESUMO

BACKGROUND: HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. METHODS: We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. RESULTS: HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. CONCLUSIONS: Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample.


Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Mutação , Inibidores de Proteases/uso terapêutico , Adulto , Brasil , Coinfecção , Feminino , Infecções por HIV , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Resultado do Tratamento , Carga Viral , Proteínas não Estruturais Virais/genética
17.
Liver Int ; 32(5): 803-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22136395

RESUMO

BACKGROUND: Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation. AIMS: To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. METHODS: We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. -318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer. RESULTS: Eight AT repetitions in 3'UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62). CONCLUSION: CTLA-4 gene polymorphisms were associated to HCV-infection. Eight AT repetitions were more prevalent in HCV-infected subjects. -318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3'UTR region favoured severe necroinflammatory activity scores in liver biopsies.


Assuntos
Antígeno CTLA-4/genética , Predisposição Genética para Doença , Hepatite C Crônica/genética , Polimorfismo de Nucleotídeo Único , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Estudos Prospectivos , Fatores de Risco
18.
Rev Panam Salud Publica ; 13(6): 376-86, 2003 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-12880518

RESUMO

OBJECTIVE: This research had two objectives: (1) to determine the prevalence of iron-deficiency anemia and describe iron consumption in the diet of schoolchildren and adolescents enrolled in public and private schools of the urban area of the city of Medellín, Colombia, in the 1999-2000 school year and (2) to explore the associations that age group, sex, socioeconomic class, and intestinal parasitism show with iron-deficiency anemia and iron deficiency. METHODS: A cross-sectional study was carried out among 960 students from 6 to 18 years old who were selected by simple random sampling after stratified multistage sampling and clustering in public and private schools in districts of Medellín. Body iron content was evaluated by determining ferritin and hemoglobin levels, average corpuscular volume, and amplitude of the erythrocyte distribution; the presence of intestinal parasites was evaluated through stool analysis; nutritional status was evaluated by means of anthropometric measurements; and consumption of iron and vitamin C was evaluated using a semiquantitative questionnaire on food intake. In order to define the cases of iron-deficiency anemia and of iron deficiency we used the standard definitions of the World Health Organization, based on ferritin and hemoglobin values. We used nonparametric tests, with a significance level of 0.05, to examine the associations between age group, sex, socioeconomic class, and the presence of intestinal parasites on the one hand and the presence of anemia on the other hand. RESULTS: The prevalence of iron deficiency was 4.9%, and the prevalence of iron-deficiency anemia was 0.6%. The prevalence of both was higher among adolescent women (P < 0.05) than in the rest of the sample studied. No significant association was found between the presence of intestinal parasites and the presence of anemia. The average daily consumption of iron (+/- standard deviation) was 5.5 mg (+/- 2.3 mg) (32% +/- 15% of the recommended dietary intake for the studied age group); the average contribution of serum iron in the diet was 0.7 mg (+/- 0.7 mg). Comparing the children who did and who did not have anemia, there were no significant differences in iron consumption and the type of iron consumed. The anthropometric parameter that showed the greatest association with the presence of anemia was height for age. CONCLUSIONS: The prevalences of iron deficiency and of iron-deficiency anemia found in the population studied were low, according to the parameters for hemoglobin and ferritin as defined by the World Health Organization as being normal for these population groups. The low prevalence of blood-sucking parasites, adequate consumption of vitamin C, and the refined mechanisms with which the body regulates iron homeostasis may have contributed to these results. Adequate iron content in the diet of adolescents should be maintained, and education campaigns should be implemented to help prevent iron deficiency in this population group.


Assuntos
Anemia Ferropriva/epidemiologia , Adolescente , Antropometria , Criança , Serviços de Saúde da Criança/estatística & dados numéricos , Colômbia/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Fatores Socioeconômicos
19.
Rev. panam. salud pública ; 13(6): 376-386, jun. 2003. tab
Artigo em Espanhol | LILACS | ID: lil-343039

RESUMO

OBJETIVO: Determinar la prevalencia de anemia ferropénica y describir el consumo de hierro en la dieta de escolares y adolescentes matriculados en colegios oficiales y privados de la zona urbana de la ciudad de Medellín, Colombia, en el año escolar 1999­2000, así como explorar la asociación entre grupo de edad, sexo, clase socioeconómica y parasitismo intestinal por un lado, y anémica ferropénica y deficiencia de hierro por el otro. MÉTODOS: Se realizó un estudio de corte transversal en 960 estudiantes de 6 a 18 años de edad que fueron elegidos por muestreo aleatorio simple tras un muestreo polietápico estratificado y por conglomerados de colegios oficiales y privados en comunas de la zona de Medellín. Se evaluaron el contenido corporal de hierro mediante determinaciones de ferritina, hemoglobina, volumen corpuscular medio y amplitud de la distribución eritrocitaria; la presencia de parásitos intestinales mediante análisis coprológico; el estado nutricional por medio de mediciones antropométricas; y el consumo de hierro y vitamina C mediante un cuestionario semicuantitativo de ingesta alimentaria. Para definir los casos de anemia ferropénica y de deficiencia de hierro se usaron las definiciones estándar de la Organización Mundial de la Salud basadas en los valores de ferritina y hemoglobina. También se examinó la asociación entre grupo de edad, sexo, clase socioeconómica y presencia de parásitos intestinales por un lado y la presencia de anemia por el otro mediante pruebas no paramétricas con un nivel de significación de 0,05. RESULTADOS: La prevalencia de deficiencia de hierro fue de 4,9 por ciento y la de anemia ferropénica, de 0,6 por ciento. Se encontró una mayor prevalencia de ambas en mujeres adolescentes (P < 0,05) que en el resto de la muestra estudiada. No se demostró ninguna asociación significativa entre la presencia de parásitos intestinales y la de anemia. El consumo promedio de hierro diario fue de 5,5 ±2,3 mg (desviación estándar [DE]) (32 por ciento ±15 por ciento [DE] de la ingesta dietética recomendada [RDA] para el grupo de edad estudiado); el aporte promedio de hierro hemático en la dieta fue de 0,7 ±0,7 mg [DE]. No se encontraron diferencias significativas en la cantidad y el tipo de hierro consumido entre los niños con y sin anemia. El parámetro antropométrico que mostró la mayor asociación con la presencia de anemia fue la relación entra la estatura y la edad...


Objective. This research had two objectives: (1) to determine the prevalence of irondeficiency anemia and describe iron consumption in the diet of schoolchildren and adolescents enrolled in public and private schools of the urban area of the city of Medellín, Colombia, in the 1999­2000 school year and (2) to explore the associations that age group, sex, socioeconomic class, and intestinal parasitism show with irondeficiency anemia and iron deficiency. Methods. A cross-sectional study was carried out among 960 students from 6 to 18 years old who were selected by simple random sampling after stratified multistage sampling and clustering in public and private schools in districts of Medellín. Body iron content was evaluated by determining ferritin and hemoglobin levels, average corpuscular volume, and amplitude of the erythrocyte distribution; the presence of intestinal parasites was evaluated through stool analysis; nutritional status was evaluated by means of anthropometric measurements; and consumption of iron and vitamin C was evaluated using a semiquantitative questionnaire on food intake. In order to define the cases of iron-deficiency anemia and of iron deficiency we used the standard definitions of the World Health Organization, based on ferritin and hemoglobin values. We used nonparametric tests, with a significance level of 0.05, to examine the associations between age group, sex, socioeconomic class, and the presence of intestinal parasites on the one hand and the presence of anemia on the other hand. Results. The prevalence of iron deficiency was 4.9%, and the prevalence of irondeficiency anemia was 0.6%. The prevalence of both was higher among adolescent women (P < 0.05) than in the rest of the sample studied. No significant association was found between the presence of intestinal parasites and the presence of anemia. The average daily consumption of iron (± standard deviation) was 5.5 mg (± 2.3 mg) (32% ± 15% of the recommended dietary intake for the studied age group); the average contribution of serum iron in the diet was 0.7 mg (± 0.7 mg). Comparing the children who did and who did not have anemia, there were no significant differences in iron consumption and the type of iron consumed. The anthropometric parameter that showed the greatest association with the presence of anemia was height for age. Conclusions. The prevalences of iron deficiency and of iron-deficiency anemia found in the population studied were low, according to the parameters for hemoglobin and ferritin as defined by the World Health Organization as being normal for these population groups. The low prevalence of blood-sucking parasites, adequate consumption of vitamin C, and the refined mechanisms with which the body regulates iron homeostasis may have contributed to these results. Adequate iron content in the diet of adolescents should be maintained, and education campaigns should be implemented to help prevent iron deficiency in this population group


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Anemia Ferropriva/epidemiologia , Antropometria , Serviços de Saúde da Criança/estatística & dados numéricos , Colômbia/epidemiologia , Estudos Transversais , Prevalência , Fatores Socioeconômicos
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