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1.
Viruses ; 16(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38932214

RESUMO

Human adenovirus-36 (HAdV-36) infection has been linked to obesity, low lipid levels, and improvements in blood glucose levels and insulin sensitivity in animal models and humans, although epidemiological studies remain controversial. Therefore, this study investigated the relationship between HAdV-36 seropositivity and glycemic control in youths. This observational study examined 460 youths (246 with normal weight and 214 obese subjects). All participants underwent assessments for anthropometry, blood pressure, circulating fasting levels of glucose, lipids, insulin, and anti-HAdV-36 antibodies; additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. In all, 57.17% of the subjects were HAdV-36 seropositive. Moreover, HAdV-36 seroprevalence was higher in obese subjects compared to their normal weight counterparts (59% vs. 55%). BMI (33.1 vs. 32.3 kg/m2, p = 0.03), and waist circumference (107 vs. 104 cm, p = 0.02), insulin levels (21 vs. 16.3 µU/mL, p = 0.003), and HOMA-IR (4.6 vs. 3.9, p = 0.02) were higher in HAdV-36-positive subjects with obesity compared to seronegative subjects. In the obese group, HAdV-36 seropositivity was associated with a reducing effect in blood glucose levels in a model adjusted for total cholesterol, triglyceride levels, age and sex (ß = -10.44, p = 0.014). Furthermore, a statistically significant positive relationship was observed between HAdV-36 seropositivity and insulin levels in the obesity group. These findings suggest that natural HAdV-36 infection improves glycemic control but does not ameliorate hyperinsulinemia in obese subjects.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Glicemia , Resistência à Insulina , Insulina , Obesidade , Humanos , Masculino , Feminino , Glicemia/análise , Insulina/sangue , Adolescente , Obesidade/sangue , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , Criança , Estudos Soroepidemiológicos , Adulto Jovem , Índice de Massa Corporal , Anticorpos Antivirais/sangue
2.
Viruses ; 16(6)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38932286

RESUMO

Background: Previous infection with Adenovirus-36 (HAdv-D36) has been associated with adipogenesis and glycemic regulation in cell culture and animal models. In humans, HAdv-D36 antibodies correlate with increased obesity risk yet paradoxically enhance glycemic control across various demographics. This study assesses the association of HAdv-D36 seropositivity with obesity, lipid, and glycemic profiles among school-aged children. Methods: We evaluated 208 children aged 9-13, categorized by BMI z-scores into normal weight (-1 to +1), overweight (+1 to +2), and obese (>+3). Assessments included anthropometry, Tanner stage for pubertal development, and biochemical tests (relating to lipids, glucose, and insulin), alongside HAdv-D36 seropositivity checked via ELISA. Insulin resistance was gauged using Chilean pediatric criteria. Results: The cohort displayed a high prevalence of overweight/obesity. HAdv-D36 seropositivity was 5.4%, showing no correlation with nutritional status. Additionally, no link between HAdv-D36 seropositivity and lipid levels was observed. Notably, insulin levels and HOMA-RI were significantly lower in HAdv-D36 positive children (p < 0.001). No cases of insulin resistance were reported in the HAdv-D36 (+) group in our population. Conclusions: HAdv-D36 seropositivity appears to decrease insulin secretion and resistance, aligning with earlier findings. However, no association with obesity development was found in the child population of southern Chile.


Assuntos
Adenovírus Humanos , Resistência à Insulina , Humanos , Chile/epidemiologia , Criança , Masculino , Feminino , Adolescente , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , Infecções por Adenovirus Humanos/sangue , Anticorpos Antivirais/sangue , Obesidade/epidemiologia , Obesidade/virologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/virologia , Estudos Soroepidemiológicos , Insulina/sangue , Prevalência , Fatores de Risco
3.
Front Immunol ; 12: 691879, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163488

RESUMO

Increasing human Adenovirus (HAdV) infections complicated with acute respiratory distress syndrome (ARDS) even fatal outcome were reported in immunocompetent adolescent and adult patients. Here, we characterized the cytokine/chemokine expression profiles of immunocompetent patients complicated with ARDS during HAdV infection and identified biomarkers for disease severity/progression. Forty-eight cytokines/chemokines in the plasma samples from 19 HAdV-infected immunocompetent adolescent and adult patients (ten complicated with ARDS) were measured and analyzed in combination with clinical indices. Immunocompetent patients with ARDS caused by severe acute respiratory disease coronavirus (SARS-CoV)-2, 2009 pandemic H1N1 (panH1N1) or bacteria were included for comparative analyses. Similar indices of disease course/progression were found in immunocompetent patients with ARDS caused by HAdV, SARS-CoV-2 or panH1N infections, whereas the HAdV-infected group showed a higher prevalence of viremia, as well as increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK). Expression levels of 33 cytokines/chemokines were increased significantly in HAdV-infected patients with ARDS compared with that in healthy controls, and many of them were also significantly higher than those in SARS-CoV-2-infected and panH1N1-infected patients. Expression of interferon (IFN)-γ, interleukin (IL)-1ß, hepatocyte growth factor (HGF), monokine induced by IFN-γ (MIG), IL-6, macrophage-colony stimulating factor (M-CSF), IL-10, IL-1α and IL-2Ra was significantly higher in HAdV-infected patients with ARDS than that in those without ARDS, and negatively associated with the ratio of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2). Analyses of the receiver operating characteristic curve (ROC) showed that expression of IL-10, M-CSF, MIG, HGF, IL-1ß, IFN-γ and IL-2Ra could predict the progression of HAdV infection, with the highest area under the curve (AUC) of 0.944 obtained for IL-10. Of note, the AUC value for the combination of IL-10, IFN-γ, and M-CSF reached 1. In conclusion, the "cytokine storm" occurred during HAdV infection in immunocompetent patients, and expression of IL-10, M-CSF, MIG, HGF, IL-1ß, IFN-γ and IL-2Ra was closely associated with disease severity and could predict disease progression.


Assuntos
Infecções por Adenovirus Humanos/sangue , Citocinas/sangue , Síndrome do Desconforto Respiratório/sangue , Infecções por Adenovirus Humanos/complicações , Infecções por Adenovirus Humanos/patologia , Adenovírus Humanos , Adolescente , Adulto , Bactérias , Infecções Bacterianas/sangue , Infecções Bacterianas/complicações , Infecções Bacterianas/patologia , Biomarcadores/sangue , COVID-19/sangue , COVID-19/complicações , COVID-19/patologia , Progressão da Doença , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/sangue , Influenza Humana/complicações , Influenza Humana/patologia , Masculino , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/patologia , SARS-CoV-2 , Índice de Gravidade de Doença , Viremia/sangue , Viremia/complicações , Viremia/patologia , Adulto Jovem
4.
Eur J Med Res ; 26(1): 45, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990223

RESUMO

BACKGROUND: Hematological comparison of coronavirus disease (COVID-19) and other viral pneumonias can provide insights into COVID-19 treatment. METHODS: In this retrospective case-control single-center study, we compared the data of 126 patients with viral pneumonia during different outbreaks [severe acute respiratory syndrome (SARS) in 2003, influenza A (H1N1) in 2009, human adenovirus type 7 in 2018, and COVID-19 in 2020]. RESULTS: One of the COVID-19 characteristics was a continuous decline in the hemoglobin level. The neutrophil count was related to the aggravation of COVID-19 and SARS. Thrombocytopenia occurred in patients with SARS and severe COVID-19 even at the recovery stage. Lymphocytes were related to the entire course of adenovirus infection, recovery of COVID-19, and disease development of SARS. CONCLUSIONS: Dynamic changes in hematological counts could provide a reference for the pathogenesis and prognosis of pneumonia caused by respiratory viruses in clinics.


Assuntos
Infecções por Adenovirus Humanos/sangue , COVID-19/sangue , Influenza Humana/sangue , Pneumonia Viral/sangue , Síndrome Respiratória Aguda Grave/sangue , Infecções por Adenovirus Humanos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/patologia , Estudos de Casos e Controles , Feminino , Hemoglobinas/análise , Humanos , Influenza Humana/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/patologia , Trombocitopenia/patologia , Adulto Jovem
5.
BMC Infect Dis ; 21(1): 213, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632148

RESUMO

BACKGROUND: Previous studies have demonstrated an association between adenovirus viremia and disease severity in immunocompromised children. However, few studies have focused on this association in immunocompetent children. This study explored the association between adenovirus viremia and adenovirus pneumonia severity in immunocompetent children. METHODS: We performed a retrospective, observational study of immunocompetent children with adenovirus pneumonia admitted to Shenzhen Children's Hospital in Shenzhen, China. Pneumonia was classified as severe or mild based on the Chinese guideline for the classification of pneumonia severity. Serum samples from all the children included in the study were tested for adenovirus DNA with a quantitative polymerase chain reaction. Clinical manifestations, laboratory examinations, and disease severity were compared between children with severe and mild pneumonia. RESULTS: A total of 111 immunocompetent children with adenovirus pneumonia (60 severe, 51 mild) were included. The median age was 40 months, and 64 patients were male. Five patients were admitted to the intensive care unit, and two underwent endotracheal intubation. All patients were discharged after recovery or improvement. Univariate analysis and binary logistic regression analysis showed that leukocytosis (OR = 1.1; 95% CI: 1.0 to 1.2; P = 0.033), co-infection with Mycoplasma pneumoniae (OR = 5.0; 95% CI: 2.1 to 12.3; P <  0.001), and high blood viral load (OR = 1.5; 95% CI: 1.2 to 2.0; P = 0.001) may be risk factors for severe adenovirus pneumonia. CONCLUSIONS: Leukocytosis, co-infection with Mycoplasma pneumoniae, and high blood viral load may be risk factors for severe adenovirus pneumonia in immunocompetent children. Blood viral load may predict pneumonia severity.


Assuntos
Adenoviridae/fisiologia , Infecções por Adenovirus Humanos/virologia , Pneumonia Viral/virologia , Viremia/virologia , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Hospitais Pediátricos , Humanos , Lactente , Masculino , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Carga Viral , Viremia/epidemiologia
6.
Virol J ; 17(1): 193, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302983

RESUMO

BACKGROUND: The new emerging coronavirus disease 2019 (COVID-19) overall shares similar symptoms with other common respiratory viral infections. We aimed in this study to compare COVID-19 and human adenovirus (HAdV) infections in pediatric patients regarding the frequencies of major clinical symptoms and the potential disparities in laboratory and imaging parameters. METHODS: Following a case-control-like design, we built 72 age-matched pediatric COVID-19 and HAdV patient pairs. Their early symptoms and laboratory and imaging characteristics were then retrieved and compared. RESULTS: Fever and cough were the most common symptoms for both infections but were seen more often in HAdV than in COVID-19 patients (92% vs. 66% and 60% vs. 18%, respectively). Compared with COVID-19 patients, children with HAdV infection had statistically significantly higher values of neutrophil count, neutrophil percentage, activated partial thromboplastin time, prothrombin time, lactate dehydrogenase, C-reactive protein, procalcitonin but lower values of lymphocyte percentage, total bilirubin, potassium and sodium. Thoracic computed tomography also revealed more anomalies in HAdV patients than in COVID-19 patients (95% vs. 67%). CONCLUSIONS: COVID-19 is an overall less symptomatic and less severe infection at admission compared to HAdV respiratory infection in pediatric population.


Assuntos
Infecções por Adenovirus Humanos/patologia , COVID-19/patologia , SARS-CoV-2 , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/diagnóstico por imagem , Adenovírus Humanos , COVID-19/sangue , COVID-19/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Tomografia Computadorizada por Raios X
7.
Genet Test Mol Biomarkers ; 24(12): 761-770, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33270503

RESUMO

Objective: To study the relationships between single nucleotide polymorphisms (SNPs) in the intron of the tumor necrosis factor α (TNFα) gene and the susceptibility and severity of disease associated with adenovirus infection in children. Methods: Four polymorphic loci of the TNFα gene (rs3093661, rs1800610, rs3093662, and rs3093664) were characterized allelically and genotypically in 320 children with adenovirus-associated pneumonia (AP) and compared with 320 healthy controls. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the plasma TNFα protein levels in all subjects. Results: The TNFα gene rs3093661 locus A allele, the rs1800610 locus A allele, the rs3093662 locus G allele, and the rs3093664 locus G allele were identified as susceptibility alleles for development of AP, and they were also positively correlated with the severity of AP. In children who had the GGAA haplotype, AP susceptibility was significantly reduced (0.28-fold) (95% confidence interval, CI: 0.20-0.40, p < 0.001). Conversely, among the subjects with the AGGG haplotype, their AP susceptibility risk was significantly increased (2.76-fold) (95% CI: 1.77-4.29, p < 0.001); and in the subjects with the AP GGGG haplotype their AP susceptibility risk was significantly increased (2.49-fold) (95% CI: 1.67-3.72, p < 0.001). The TNFα rs3093661, rs1800610, rs3093662, and rs3093664 SNPs were significantly correlated with plasma TNFα levels (p < 0.05). Conclusion: The TNFα gene rs3093661, rs1800610, rs3093662, and rs3093664 loci are associated with AP susceptibility and severity. This relationship might be due to the effect on TNFα levels found in the plasma. Clinical Trial Registration number: LL20190723.


Assuntos
Infecções por Adenovirus Humanos/genética , Pneumonia Viral/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Infecções por Adenovirus Humanos/sangue , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Reações Falso-Positivas , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Lactente , Masculino , Pneumonia Viral/sangue , Risco , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue
8.
Biomed Res Int ; 2020: 4878635, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802848

RESUMO

PURPOSE: The aim of this work was to analyze clinical features and laboratory findings of children with adenovirus pneumonia and guide clinical diagnosis, treatment, and assessment of disease severity. Material and Methods. Retrospective analysis of clinical data of 285 children with adenoviral pneumonia who were hospitalized in Wuhan Children's Hospital from December 2018 to October 2019. According to the assessment criteria for severe pneumonia, it was divided into the severe group (92 cases) and the nonsevere group (193 cases). Collected clinical manifestations, complications, and laboratory test indicators in two groups of children and conducted all statistical analyses. RESULTS: The risk of fever and wheezing was significantly higher in the severe group than in the nonsevere group. The difference was statistically significant (P < 0.05). The risk of complications in the severe group was significantly higher than that in the nonsevere group. The difference was statistically significant (P < 0.05). The levels of AST, LDH-L, PCT, ferritin, and D-dimer in the severe group were significantly higher than those in the nonsevere group. The difference was statistically significant (P < 0.05). CONCLUSION: Children with severe adenovirus pneumonia have severe clinical manifestations and many complications. AST, LDH-L, PCT, ferritin, and D-dimer levels have important clinical implications for assessing disease severity.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos/metabolismo , Pneumonia Viral , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/epidemiologia , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
9.
Front Immunol ; 11: 614781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33542721

RESUMO

Background: Human adenoviruses (HAdV) infection caused pneumonia remains a major threat to global children health. Currently, diagnosis of severe HAdV pneumonia in children is hampered by the lack of specific biomarkers. Also, the severity of adenovirus pneumonia in pediatric patients is generally based on clinical features and existing biomarkers do not reliably correlate to clinical severity. Here, we asked whether local and systemic inflammatory mediators could act as biomarkers predicting severe HAdV pneumonia in children. Methods: Totally 37 common inflammatory protein levels were determined by Luminex assay in plasma and bronchoalveolar lavage (BAL) from pediatric patients who were diagnosed with HAdV pneumonia, and their correlation with the disease severity and lung lesion were assessed using statistical and bioinformatic analysis. Results: Among 37 inflammatory cytokines, the protein levels of 4 TNF superfamily (TNFSF) members and their receptors (TNF receptor superfamily, TNFRSF) [TNFSF13B, TNFSF14, sTNF-R1 and sTNF-R2] in the plasma and 7 TNFSF/TNFRSF members [TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFRSF8, sTNF-R1, and sTNF-R2] in the BAL were enhanced in patients with HAdV pneumonia compared with control subjects with airway foreign body. Moreover, the protein levels of all the tested TNFSF/TNFRSF members (except TNFSF12) were elevated in the BAL of severe group compared with non-severe HAdV pneumonia patients, while only TNFSF13B and TNFSF14 were dramatically increased in the plasma of severe cases, and positively related to the plasma CRP levels. In addition, ROC analysis indicated that TNFSF13B and TNFSF14 displayed a great potential to predict severe HAdV pneumonia. Conclusion: In pediatric HAdV pneumonia, TNFSF/TNFRSF members function as key molecules in local and systemic inflammatory network, and the plasma TNFSF13B and TNFSF14 may be the potential local and systemic inflammatory indicators of severe HAdV pneumonia in pediatric patients.


Assuntos
Infecções por Adenovirus Humanos/sangue , Fator Ativador de Células B/sangue , Pneumonia Viral/sangue , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Infecções por Adenovirus Humanos/diagnóstico por imagem , Infecções por Adenovirus Humanos/fisiopatologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/isolamento & purificação , Biomarcadores/sangue , Lavagem Broncoalveolar , Broncoscopia , Criança , Pré-Escolar , Estudos de Coortes , Citocinas/sangue , Regulação para Baixo , Feminino , Humanos , Imunoensaio , Lactente , Inflamação/sangue , Masculino , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Regulação para Cima
10.
Transpl Infect Dis ; 22(1): e13238, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31880047

RESUMO

Adenovirus is an infrequent but challenging viral complication of transplantation that is rarely reported after autologous stem cell transplant. We present a case of disseminated adenovirus infection in a woman who received an autologous stem cell transplant for treatment of multiple sclerosis. After presenting with post-transplant episodic diarrhea and viremia, endoscopic biopsies and immunohistochemical staining confirmed the diagnosis of disseminated adenovirus infection. Her symptoms and viremia resolved after treatment with cidofovir. This case demonstrates that a high index of suspicion, a systematic clinical approach, and immunohistochemical tissue staining are necessary to diagnose disseminated adenovirus infection in an unexpected host.


Assuntos
Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Esclerose Múltipla/terapia , Viremia/etiologia , Adenoviridae , Infecções por Adenovirus Humanos/tratamento farmacológico , Antivirais/uso terapêutico , Cidofovir/uso terapêutico , Colo/virologia , Diarreia/virologia , Duodeno/virologia , Endoscopia , Feminino , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Transplante Autólogo/efeitos adversos , Carga Viral/efeitos dos fármacos
11.
J Clin Microbiol ; 57(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31434723

RESUMO

Adenoviruses (AdV) have been associated with a variety of human diseases and are recognized as causing significant morbidity and mortality in immunocompromised or transplant patients. Quantification of AdV DNA in plasma is notoriously difficult due to the genetic diversity of the 71 different serotypes identified to date. There is no World Health Organization standard available to harmonize quantitative data, so results between labs vary widely. In this study, we compared a laboratory-developed multiplex PCR assay with primers and probes specific for each group (A to G) and subgroup E4 (Octaplex) to one with a single primer and probe set (modified from N. Jothikumar et al., Appl Environ Microbiol 71:3131-3136, 2005) and one utilizing bisulfite pretreatment of DNA to reduce variation prior to amplification (Genetic Signatures). Our Octaplex assay detected all low-copy-number clinical samples, while the other two assays had subsets of samples that did not amplify. The modified Jothikumar assay failed to efficiently amplify three of the high-copy-number cultured strains, while the Genetic Signatures 3base assay had a positive bias, resulting in higher copies/ml (>0.5 log10) for all culture fluids tested. All three assays resulted in endpoint detection of the available 51 AdV types. Using two different materials to generate a standard curve revealed that the Octaplex TaqMan assay and the modified Jothikumar assay both consistently gave adenovirus levels lower than the commercial platform for AdV culture fluids but not patient samples. This study highlights the differences in detection of AdV between laboratories that can be attributed to both the PCR method, as well as the reference material used for quantitation.


Assuntos
Infecções por Adenovirus Humanos/diagnóstico , Adenovírus Humanos/isolamento & purificação , Primers do DNA/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções por Adenovirus Humanos/sangue , Adenovírus Humanos/classificação , Sondas de DNA/genética , DNA Viral/genética , Variação Genética , Humanos , Sensibilidade e Especificidade
13.
J Clin Virol ; 111: 19-23, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30594701

RESUMO

BACKGROUND: Human adenovirus (HAdV) is a double-stranded DNA virus associated with respiratory tract infections (RTI) in children. Using polymerase chain reaction (PCR) tests, HAdV often is detected together with other virus species, even in healthy controls. OBJECTIVES: The aim of this study was to compare molecular detection of HAdV with culture, and to examine the associations of various methods to RTI. STUDY DESIGN: Nasopharyngeal aspirates (NPA) were collected from 4319 children admitted with RTI and from 361 controls. The NPAs were examined for 23 viral and bacterial pathogens, using inhouse real-time PCR-assays based on TaqMan probes, in addition to bacterial and viral culture. HAdV concentration was evaluated semi-quantitatively from the Ct-value and quantitatively by use of ADENOVIRUS R-gene®. RESULTS: HAdV-DNA was detected in 6.1% patient samples and in 10.5% controls (p< 0.001). Compared to controls, patients had an OR of 3.8 (95% CI 1.4-10.3) for mono-detection of HAdV DNA, and an OR of 5.1 (95% CI 2.0-13.4) for HAdV-positive samples grew adenovirus by culture. HAdV DNA loads from children with RTI consisted of two clusters: one cluster with high viral loads (Ct < 30 and >106 copies/ml) and one cluster with low viral loads, whereas among the controls, nearly all had low viral loads (OR 7.8, 95% CI 2.2-27.1). In 61 available plasma samples, 16.4% were positive for HAdV DNA, all were from patients. CONCLUSION: The detection of HAdV DNA per se by qualitative PCR is not useful as a diagnostic test. Detection of HAdV by use of viral culture and a high viral HAdV DNA load are the two methods most strongly associated with RTI in children.


Assuntos
Infecções por Adenovirus Humanos/sangue , Adenovírus Humanos/isolamento & purificação , Nasofaringe/virologia , Infecções Respiratórias/virologia , Cultura de Vírus , Infecções por Adenovirus Humanos/diagnóstico , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , DNA Viral/análise , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase , Carga Viral/métodos
14.
Artigo em Inglês | MEDLINE | ID: mdl-30524972

RESUMO

Human adenovirus (HAdV) infections are well-described after hematopoietic stem cell transplantation but less well understood in solid organ transplantation (SOT). We describe a case of disseminated HAdV type 21 infection 5 months after combined liver-kidney transplantation, expanding the limited literature describing this infection in the SOT population.


Assuntos
Infecções por Adenovirus Humanos/transmissão , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/tratamento farmacológico , Infecções por Adenovirus Humanos/urina , Adenovírus Humanos/genética , Antivirais , DNA Viral , Humanos , Urina/virologia , Carga Viral , Viremia/virologia
15.
Med Sci Monit ; 24: 3848-3855, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29877315

RESUMO

BACKGROUND The aim of this study was to characterize adenovirus-associated acute respiratory infection (ARI) and observe correlations between inflammatory markers and severity of human adenovirus type 7 (HAdV-7) infection, and to evaluate the potential of inflammatory markers to predict progression from upper-respiratory infection (URI) to adenovirus pneumonia (AdP). MATERIAL AND METHODS A total of 81 patients with adenovirus-associated ARI and confirmed HAdV-7 infection were enrolled. Cases were classified according to severity, as AdP and URI. Demographic and clinical data were collected retrospectively. Clinical features and serum inflammatory markers were evaluated and compared according to the severity of adenoviral infection. RESULTS We observed high-grade fever and strong inflammatory response in patients with HAdV-7-associated ARI. Procalcitonin (PCT), interleukin 6 (IL-6), and C-reactive protein concentrations were higher in patients with AdP than in those with URI. The mean erythrocyte sedimentation rate (ESR) was significantly higher in patients with AdP (p=0.008). Reduced serum prealbumin levels were observed in patients with HAdV-7 infection. In the analysis of URI to AdP prediction ability, areas under the curve (AUCs) for all inflammatory markers were <0.9. We found that 35.9% of pneumonia had ≥2 lobars of lung infiltrate and bilateral lung infiltrate, and 20% of patients with SP had pleural effusion and atelectasis. CONCLUSIONS IL-6 and ESR were associated with the severity of HAdV-7 respiratory infection. No inflammatory marker in our study predicted URI-to-AdP progression accurately. Lung infiltration and consolidation are common in HRCT in AdP. Multiple- or single-lobar/segment consolidation was most common in SP. SP progressed very quickly after onset.


Assuntos
Infecções por Adenovirus Humanos/metabolismo , Infecções Respiratórias/metabolismo , Adenoviridae/metabolismo , Infecções por Adenovirus Humanos/sangue , Adenovírus Humanos , Adolescente , Adulto , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Calcitonina/sangue , Estudos de Coortes , Feminino , Humanos , Interleucina-6/sangue , Pulmão/metabolismo , Masculino , Infecções Respiratórias/sangue , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
16.
Transpl Infect Dis ; 20(3): e12885, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29569813

RESUMO

BACKGROUND: Epidemiologic studies of human adenovirus (HAdV) in allogeneic hematopoietic cell transplantation (HCT) recipients have been conducted mostly in European countries where HAdV 2 (species C) has been most prevalent in the community. The main objective of this study was to investigate the epidemiology and the characteristics of HAdV infection in Korean allogeneic HCT recipients (<19 years). METHODS: In a prospective study from April 2012 to September 2015, HAdV in blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected. HAdV infection was defined as positive HAdV PCR result in any specimens regardless of symptoms. RESULTS: A total of 1734 specimens were collected from 57 consecutively enrolled recipients. The cumulative incidence of HAdV infection at day 100, and 1 year was 10%, and 20%, and the incidence of viremia was 2% and 6%, respectively. The median onset time from HCT to viremia was 221 days (range, 7-596 days). All viremia cases were caused by only HAdV 3 (species B), whereas several types were detected in stool. Among patients with HAdV infection, lower absolute lymphocyte counts and extensive chronic graft-vs-host disease were associated with viremia (P = .028 and P = .006, respectively). CONCLUSIONS: Compared to western studies, this study demonstrated a lower incidence and delayed onset of HAdV infections and HAdV 3 was most prevalent in Korea.


Assuntos
Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Adenovirus Humanos/urina , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/classificação , Adolescente , Criança , Pré-Escolar , DNA Viral/sangue , Fezes/virologia , Feminino , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Incidência , Lactente , Contagem de Linfócitos , Masculino , Estudos Prospectivos , República da Coreia/epidemiologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/estatística & dados numéricos , Carga Viral , Viremia
17.
J Hematol Oncol ; 10(1): 102, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28482908

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). METHODS: Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. RESULTS: One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. CONCLUSIONS: Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).


Assuntos
Infecções por Adenovirus Humanos/terapia , Adenovírus Humanos/imunologia , Imunoterapia Adotiva/métodos , Subpopulações de Linfócitos T/transplante , Viremia/terapia , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/prevenção & controle , Adolescente , Adulto , Aloenxertos , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Separação Imunomagnética , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Interferon gama/metabolismo , Leucaférese , Masculino , Especificidade do Receptor de Antígeno de Linfócitos T , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Doadores de Tecidos , Transplante Haploidêntico , Resultado do Tratamento , Carga Viral , Ativação Viral , Adulto Jovem
18.
Transpl Infect Dis ; 18(5): 791-794, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27482652

RESUMO

Infections with adenovirus (AdV) and herpesviruses can result in considerable morbidity and mortality in pediatric hematopoietic stem cell transplant (SCT) recipients. Herpes simplex virus (HSV) reactivations are usually prevented by acyclovir (ACV) prophylaxis, whereas cidofovir (CDV) has been used off indication to manage AdV infections. We report a child with myelodysplastic syndrome undergoing multiple SCT, who experienced HSV-1 disease including severe mucositis and herpetic whitlow, as well as high viral load AdV DNAemia. Both ACV and CDV were ineffective; however, viral loads were decreased with brincidofovir, resulting in viral clearance. A subsequent Epstein-Barr virus disease with relevant meningoencephalitis responded to rituximab.


Assuntos
Adenoviridae/fisiologia , Infecções por Adenovirus Humanos/tratamento farmacológico , Antivirais/uso terapêutico , Citosina/análogos & derivados , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Simples/tratamento farmacológico , Herpes Zoster/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , Mucosite/tratamento farmacológico , Síndromes Mielodisplásicas/cirurgia , Organofosfonatos/uso terapêutico , Aciclovir/administração & dosagem , Aciclovir/uso terapêutico , Adenoviridae/isolamento & purificação , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/virologia , Antibioticoprofilaxia , Antivirais/administração & dosagem , Pré-Escolar , Cidofovir , Citosina/administração & dosagem , Citosina/uso terapêutico , DNA Viral/sangue , Farmacorresistência Viral , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/virologia , Feminino , Foscarnet/administração & dosagem , Foscarnet/uso terapêutico , Herpes Simples/virologia , Herpes Zoster/virologia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 4 , Humanos , Hospedeiro Imunocomprometido , Meningoencefalite/virologia , Mucosite/virologia , Organofosfonatos/administração & dosagem , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Carga Viral
19.
Int J Obes (Lond) ; 39(12): 1761-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26293231

RESUMO

Recent studies have suggested a possible correlation between obesity and adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA presence in human adipose tissue are limited, we evaluated the presence of Adv36 DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was extracted from adipose tissue biopsies. Virus detection was performed using PCR protocols with primers against specific Adv36 fiber protein and the viral oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the NCBI database and phylogenetic analyses were carried out with MEGA6 software. Adv36 DNA was found in four samples (19%). This study indicates that some individuals carry Adv36 in the visceral adipose tissue. Further studies are needed to determine the specific effect of Adv36 infection on adipocytes, the prevalence of Adv36 infection and its relationship with obesity in the perspective of developing a vaccine that could potentially prevent or mitigate infection.


Assuntos
Adenoviridae/isolamento & purificação , Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/isolamento & purificação , Gordura Intra-Abdominal/virologia , Obesidade/virologia , Adenoviridae/genética , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/imunologia , Adenovírus Humanos/imunologia , Adulto , Índice de Massa Corporal , DNA Viral/isolamento & purificação , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/imunologia , Filogenia
20.
J Child Neurol ; 30(7): 823-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25117415

RESUMO

Acute virus-associated encephalopathy induces seizures. Serum N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are elevated following febrile and afebrile seizures. However, the role of NTproBNP in acute virus-associated encephalopathy pathology is unknown. We enrolled 10 patients with acute virus-associated encephalopathy and convulsions (E group: 7 boys, 3 girls; median age, 3.10 ± 1.92 years) and 130 patients with febrile seizure (FS group: 80 boys, 50 girls; median age, 3.23 ± 2.44 years). The E group had significantly higher NTproBNP levels (345 ± 141 pg/mL) compared with the FS group (166 ± 228 pg/mL) (P < .0005). Furthermore, subjects with prolonged seizure within the E group had significantly higher NTproBNP levels (303 ± 107 pg/mL) compared with subjects with prolonged seizure within the FS group (134 ± 100 pg/mL) (P < .005). Our findings suggest that serum NTproBNP levels are increased during the acute phase of acute virus-associated encephalopathy associated with convulsion.


Assuntos
Infecções por Adenovirus Humanos/sangue , Encefalite Viral/sangue , Influenza Humana/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Infecções por Rotavirus/sangue , Doença Aguda , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Convulsões/sangue , Convulsões Febris/sangue
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