RESUMEN
BACKGROUND: Increasing numbers of hepatitis C virus (HCV) infections among men who have sex with men (MSM) are being observed in the Western world. The actual routes of HCV transmission during high-risk sex practices and associated drug use remain poorly understood. METHODS: Forty-seven patients with HCV were prospectively enrolled. Rectal and nasal swabs were collected to quantify HCV-RNA levels within rectal and nasal fluids. Contamination by occult rectal bleeding was excluded by guaiac paper test. Risk behavior was assessed by standardized questionnaires. RESULTS: Median age was 41.9 years, 89% were HIV positive (+) (42/47) and 85% (40/47) were male, 58% (23/40) of whom were MSM. Acute HCV infection was diagnosed in 32% (15/47) ,with all patients being HIV+MSM and 93% (14/15) having a documented history of sexually transmitted disease. Thirty-three (70%) patients had ≥1 HCV+ swab sample (HCV+SS; 48%, 22/46 rectal; 62%, 29/47 nasal), and contamination with blood was excluded in all patients. Individuals with HCV+SS had significantly higher serum HCV-RNA levels than patients with HCV-negative SS (6.28 [IQR, 0.85] log IU/mL vs 4.08 [2.45] log IU/mL; P < .001). Using ROC-curve analysis, serum HCV-RNA cutoffs for ruling in/out any HCV+SS were established at 6.02 log IU/mL and 4.02 log IU/mL, respectively. CONCLUSIONS: HCV-RNA is commonly detectable in rectal and nasal fluids of both HIV+ and HIV-negative HCV patients with high serum HCV-RNA, independently of the suspected route of HCV transmission. Accordingly, high-risk sex practices and sharing of nasal drug-sniffing "tools" might be important HCV transmission routes, especially in patients with high serum HCV-RNA.
Asunto(s)
Infecciones por VIH , Hepatitis C , Minorías Sexuales y de Género , Adulto , Femenino , Hepacivirus/genética , Homosexualidad Masculina , Humanos , Masculino , ARN , Factores de Riesgo , Viremia/diagnósticoRESUMEN
Systemic mastocytosis (SM) is characterized by abnormal accumulation of neoplastic mast cells harboring the activating KIT mutation D816V in the bone marrow and other internal organs. As found in other myeloproliferative neoplasms, increased production of profibrogenic and angiogenic cytokines and related alterations of the bone marrow microenvironment are commonly found in SM. However, little is known about mechanisms and effector molecules triggering fibrosis and angiogenesis in SM. Here we show that KIT D816V promotes expression of the proangiogenic cytokine CCL2 in neoplastic mast cells. Correspondingly, the KIT-targeting drug midostaurin and RNA interference-mediated knockdown of KIT reduced expression of CCL2. We also found that nuclear factor κB contributes to KIT-dependent upregulation of CCL2 in mast cells. In addition, CCL2 secreted by KIT D816V+ mast cells was found to promote the migration of human endothelial cells in vitro. Furthermore, knockdown of CCL2 in neoplastic mast cells resulted in reduced microvessel density and reduced tumor growth in vivo compared with CCL2-expressing cells. Finally, we measured CCL2 serum concentrations in patients with SM and found that CCL2 levels were significantly increased in mastocytosis patients compared with controls. CCL2 serum levels were higher in patients with advanced SM and were found to correlate with poor survival. In summary, we have identified CCL2 as a novel KIT D816V-dependent key regulator of vascular cell migration and angiogenesis in SM. CCL2 expression correlates with disease severity and prognosis. Whether CCL2 may serve as a therapeutic target in advanced SM remains to be determined in forthcoming studies.
Asunto(s)
Médula Ósea/patología , Quimiocina CCL2/sangre , Mastocitosis Sistémica/patología , Proteínas Proto-Oncogénicas c-kit/genética , Movimiento Celular , Microambiente Celular , Quimiocina CCL2/fisiología , Células Endoteliales/citología , Fibrosis , Humanos , Mastocitos/metabolismo , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/metabolismo , Mutación Missense , Neovascularización Patológica , PronósticoRESUMEN
The impact of excess viral RNA on myocardial function and morphology in the setting of acute human immunodeficiency virus (HIV) infection remains unknown. In this study, 49 patients with acute HIV infection showed increased levels of N-terminal prohormone of brain natriuretic peptide, a surrogate of myocardial function, which decreased with viral suppression and normalization of systemic inflammation (79 pg/mL vs 28 pg/mL; P < .001). A comparable change was seen with levels of troponin T, a marker of morphologic myocardial damage (4.9 ng/L vs 1.5 ng/L; P < .001). In conclusion, we observed significant functional and morphological myocardial impairment during acute HIV infection, fueled by inflammatory activation and extensive viral replication, resulting in a reversible subclinical inflammatory cardiomyopathy.
Asunto(s)
Cardiomiopatías/etiología , Cardiomiopatías/patología , Infecciones por VIH/patología , VIH/aislamiento & purificación , Péptido Natriurético Encefálico/sangre , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Troponina T/sangre , Carga ViralRESUMEN
BACKGROUND & AIMS: The severity of acute viral hepatitis, which may be caused by several distinct viruses, varies among individual patients. In rare cases, severe hepatic injury with sudden loss of liver function may occur, which is clinically indicated by the occurrence of coagulopathy or encephalopathy. As the molecular mechanisms of this liver injury are largely unknown, we investigated extracellular micro RNA (miRNA) profiles in 54 patients acutely infected with one of four different hepatotropic viruses, in order to identify those miRNAs which indicate severe viral hepatitis associated with coagulopathy. METHODS: First, the profile of miRNAs was extensively analysed using a microarray-based approach in highly characterized 24 patients, matched in terms of sex, age and level of liver enzymes, as well as in three healthy controls. The cohort included samples from 18 patients with moderate and six individuals with severe hepatitis, indicated by abnormal prothrombin time and higher alanine aminotransferase and bilirubin levels. miRNAs found to be upregulated in severe hepatitis were then quantified by real-time PCR in the expanded cohort of 54 patients. RESULTS: Comprehensive microarray-based miRNA profiling identified upregulation of mir-106a, mir-122 and mir-197 in patients with severe acute viral hepatitis with coagulopathy, as compared to patients who did not develop coagulopathy. mir-106a, mir-122 and mir-197 were then proven to be significantly upregulated in patients with severe acute viral hepatitis by quantitative real-time PCR (P < 0.01, Mann-Whitney U-test). CONCLUSIONS: mir-106a, mir-122 and mir-197 could be potential markers for severe acute viral hepatitis associated with coagulopathy.
Asunto(s)
Coagulación Sanguínea , Hepatitis A/genética , Hepatitis B/genética , Hepatitis C/genética , Hepatitis E/genética , MicroARNs/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Perfilación de la Expresión Génica/métodos , Hepatitis A/sangre , Hepatitis A/diagnóstico , Hepatitis B/sangre , Hepatitis B/diagnóstico , Hepatitis C/sangre , Hepatitis C/diagnóstico , Hepatitis E/sangre , Hepatitis E/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Tiempo de Protrombina , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Regulación hacia Arriba , Adulto JovenRESUMEN
Allergens and rhinovirus infections are among the most common elicitors of respiratory diseases. We report the construction of a recombinant combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived VP1, the surface protein which is critically involved in infection of respiratory cells, and a nonallergenic peptide of the major grass pollen allergen Phl p 1. Recombinant hybrid molecules consisting of VP1 and a Phl p 1-derived peptide of 31 aa were expressed in Escherichia coli. The hybrid molecules did not react with IgE Abs from grass pollen allergic patients and lacked allergenic activity when exposed to basophils from allergic patients. Upon immunization of mice and rabbits, the hybrids did not sensitize against Phl p 1 but induced protective IgG Abs that cross-reacted with group 1 allergens from different grass species and blocked allergic patients' IgE reactivity to Phl p 1 as well as Phl p 1-induced basophil degranulation. Moreover, hybrid-induced IgG Abs inhibited rhinovirus infection of cultured human epithelial cells. The principle of fusing nonallergenic allergen-derived peptides onto viral carrier proteins may be used for the engineering of safe allergy vaccines which also protect against viral infections.
Asunto(s)
Alérgenos/inmunología , Resfriado Común/prevención & control , Hipersensibilidad/prevención & control , Proteínas de Plantas/inmunología , Vacunas Sintéticas/inmunología , Proteínas Virales/inmunología , Animales , Reacciones Cruzadas/inmunología , Electroforesis en Gel de Poliacrilamida , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Ratones , Conejos , Proteínas Recombinantes de Fusión/inmunología , Rhinovirus , Vacunas Combinadas/inmunologíaAsunto(s)
Virus de la Influenza A , Virus de la Influenza B , Gripe Humana/epidemiología , Gripe Humana/virología , Austria/epidemiología , Historia del Siglo XXI , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/genética , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/historia , Coronavirus del Síndrome Respiratorio de Oriente MedioRESUMEN
Herpes simplex virus (HSV) infections can cause considerable morbidity. Currently, nucleoside analogues such as acyclovir are widely used for treatment. However, HSV infections resistant to these drugs are a clinical problem among immunocompromised patients. To provide more efficient therapy and to counteract resistance, a different class of antiviral compounds has been developed. Pritelivir, a helicase primase inhibitor, represents a promising candidate for improved therapy. Here, we established an HSV-1 infection model on microneedle-pretreated human skin ex vivo. We identified HSV-1-specific histological changes (e.g., cytopathic effects, multinucleated giant cells), down-regulation of nectin-1, nuclear translocation of NF-κB (p65), interferon regulatory factor 3 (IRF3), and signaling of the IFN-inducible protein MxA. Accordingly, this model was used to test the potency of pritelivir compared with the standard drug acyclovir. We discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. To our knowledge, we present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research.
Asunto(s)
Antivirales/farmacología , Herpes Simple/tratamiento farmacológico , Herpes Simple/patología , Herpesvirus Humano 1/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Aciclovir/farmacología , Adulto , Anciano , Biopsia con Aguja , Estudios de Casos y Controles , Femenino , Herpes Simple/virología , Herpesvirus Humano 1/aislamiento & purificación , Humanos , Inmunohistoquímica , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Modelos Biológicos , Piridinas/farmacología , Valores de Referencia , Estadísticas no Paramétricas , Sulfonamidas , Tiazoles/farmacología , Adulto JovenRESUMEN
BACKGROUND: Morbidity, severity, and mortality associated with annual influenza epidemics are of public health concern. We analyzed surveillance data on hospitalized laboratory-confirmed influenza cases admitted to intensive care units to identify common determinants for fatal outcome and inform and target public health prevention strategies, including risk communication. METHODS: We performed a descriptive analysis and used Poisson regression models with robust variance to estimate the association of age, sex, virus (sub)type, and underlying medical condition with fatal outcome using European Union data from 2009 to 2017. RESULTS: Of 13 368 cases included in the basic dataset, 2806 (21%) were fatal. Age ≥40 years and infection with influenza A virus were associated with fatal outcome. Of 5886 cases with known underlying medical conditions and virus A subtype included in a more detailed analysis, 1349 (23%) were fatal. Influenza virus A(H1N1)pdm09 or A(H3N2) infection, age ≥60 years, cancer, human immunodeficiency virus infection and/or other immune deficiency, and heart, kidney, and liver disease were associated with fatal outcome; the risk of death was lower for patients with chronic lung disease and for pregnant women. CONCLUSIONS: This study re-emphasises the importance of preventing influenza in the elderly and tailoring strategies to risk groups with underlying medical conditions.
RESUMEN
Guillain-Barré syndrome (GBS) is frequently associated with the presence of CMV-specific IgM-antibodies or CMV-DNA in serum. Detection of IgM-antibodies or viremia may indicate primary infection, but also reactivation or reinfection. We identified 46 GBS patients with detectable CMV-specific IgM- or IgG-antibodies, or both. Sera from these patients were tested for the presence of CMV-specific, low-avidity IgG-antibodies, which indicate primary infection that occurred <6 months before sample collection, and for the presence of CMV-DNA by polymerase chain reaction (PCR). Primary infection was identified by the presence of low-avidity IgG-antibodies in 9/46 (20%) or by detection of IgM-antibodies in the absence of IgG-antibodies in 1/46 (2%) patients. CMV-DNA was detectable in 17/46 (37%) sera. In contrast, CMV-DNA was detected in only 2% of sera from 46 age-matched patients with neuroborreliosis. The likelihood of viremia decreased in GBS patients significantly with increasing antibody-avidity (P=0.041). Detection of IgM-antibodies correlated with that of CMV-DNA in patients with low-avidity IgG-antibodies (P=0.048) but not in those with high-avidity IgG-antibodies (P=0.543). In 45 age-matched healthy controls, low-avidity IgG-antibodies and CMV-DNA were detected in only 2% and 0% of sera, respectively. Our findings further strengthen evidence for an association between CMV infection and GBS. Primary CMV infection was identified in almost one-fourth of patients with detectable CMV-specific antibodies. Nevertheless, endogenous reactivation and reinfection have to be considered also as relevant events associated with GBS.
Asunto(s)
Anticuerpos Antivirales/inmunología , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Síndrome de Guillain-Barré/inmunología , Síndrome de Guillain-Barré/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/líquido cefalorraquídeo , Niño , Preescolar , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/complicaciones , Femenino , Síndrome de Guillain-Barré/sangre , Síndrome de Guillain-Barré/líquido cefalorraquídeo , Síndrome de Guillain-Barré/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
Cytomegalovirus (CMV) infection was one of the most important opportunistic infections in HIV-infected patients before the introduction of highly active antiretroviral therapy (HAART), i.e. the combination of at least three antiretroviral drugs of different classes. Thereafter, life expectancy and quality of life increased dramatically with the persistent suppression of HIV viremia and a significant reduction in incidence of CMV disease. Nevertheless, evidence for a multitude of direct and indirect effects of CMV on HIV progression is accumulating. Even in the era of HAART, a considerable number of HIV-infected patients have a CD4 cell count below <100 mm(-3), which involves a high risk for CMV disease. The focus of the present review is on interpretation of test results, their predictive value for CMV disease, and guidance for the rational use of diagnostic assays in HIV-infected patients. Identification of patients at immediate risk for CMV disease may be accomplished by detection of CMV-DNA in leucocytes or plasma. Evidence is growing that CMV genotypes may be also relevant for the risk of CMV disease. Diagnosis of CMV disease requires in most instances demonstration of virus in biopsy specimen from the affected organ because presence of CMV in blood may not be causally related to symptoms observed. Clinical symptoms and patient characteristics are essential in the interpretation of laboratory test results and may guide the rational collection of clinical specimen and use of laboratory assays. As a consequence, a reliable diagnosis of CMV disease and early identification of patients at high risk for CMV disease requires an integrated interpretation of clinical and virological information.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Terapia Antirretroviral Altamente Activa , Infecciones por Citomegalovirus/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Citomegalovirus/aislamiento & purificación , ADN Viral/sangre , Genotipo , Infecciones por VIH/complicaciones , Humanos , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: The outcome of acute hepatitis C is determined by early host-virus interactions, particularly involving the antiviral T-cell response. OBJECTIVES: To identify early prognostic markers of spontaneous resolution of acute hepatitis C by performing a comprehensive analysis of viral and immunological factors during the natural course of acute HCV infection and reinfection. STUDY DESIGN: 20 patients were investigated prospectively during acute HC or confirmed reinfection and 18 of them during follow up after spontaneous or treatment-induced elimination of the virus and resolution of the disease. Multiparameter flow cytometry was used to functionally characterize virus-specific CD4(+) T-cell responses relative to the virologic outcome. RESULTS: Parallel immunologic and virologic monitoring of patients with acute HC identified distinct patterns of host-virus interaction related to HCV persistence or clearance. The highest frequency of antiviral Th1 cytokine-producing CD4(+) T-cells was observed in patients with HCV reinfection, preceding rapid viral clearance within 3 weeks after disease onset. In all patients who subsequently cleared viremia, CD4(+) T-cells produced Th1 cytokines following stimulation with non-structural HCV antigens (NS3 and NS4). In contrast, a chronic course of disease was associated with the absence of antiviral Th1 cytokine producing cells from the first weeks after onset of disease (acute persistent HC), or with fluctuating RNA levels (yo-yo pattern) and gradual waning of antiviral Th1 cells. CONCLUSIONS: The results highlight the variability of immune response pattern in acute hepatitis C. Most importantly, "acute persistent hepatitis C" and a lack of TH1 effector cells within the first months of acute hepatitis C represent efficacious predictors of viral persistence and could thus be used as criteria in selecting candidates for early antiviral treatment.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Hepacivirus/aislamiento & purificación , Hepatitis C/inmunología , Hepatitis C/virología , ARN Viral/análisis , Adolescente , Adulto , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Diseño de Software , Carga Viral , ViremiaRESUMEN
BACKGROUND: Influenza vaccine effectiveness (VE) is influenced by the antigenic similarity between vaccine- and circulating strains. MATERIAL AND METHODS: This paper presents data obtained by the Austrian sentinel surveillance system on the evolution of influenza viruses during the season 2014/15 and its impact on influenza vaccine effectiveness in primary care in Austria as estimated by a test-negative case control design. VE estimates were performed for each influenza virus type/subtype, stratified by underlying diseases and adjusted for age, sex and calendar week of infection. RESULTS: Detailed genetic and antigenic analyses showed that circulating A(H3N2) viruses were genetically distinct from the 2014/15 A(H3N2) vaccine component indicating a profound vaccine mismatch. The Influenza A(H1N1)pdm09 viruses were antigenically conserved and matched the respective vaccine component. Influenza B viruses were lineage-matched B/Yamagata viruses with a clade-level variation. Consistent with substantial vaccine mismatch for the A(H3N2) viruses a crude overall VE of only 47% was estimated, whereas the VE estimates for A(H1N1)pdm09 were 84% and for influenza B viruses 70%. Increased VE estimates were obtained after stratification by underlying diseases and adjustment for the covariates sex and age, whereby the adjustment for the calendar week of infection was the covariate exerting the highest influence on adjusted VE estimates. CONCLUSION: In summary, VE data obtained in this study underscore the importance to perform VE estimates in the context of detailed characterization of the contributing viruses and also demonstrate that the calendar week of influenza virus infection is the most important confounder of VE estimates.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Vigilancia de Guardia , Anciano , Anciano de 80 o más Años , Austria , Femenino , Humanos , Masculino , Atención Primaria de SaludRESUMEN
BACKGROUND: Different human cytomegalovirus (HCMV) strains may persistently coexist in the human host. In immunosuppressed patients infection with mixed HCMV populations was associated with a more severe course of infection. Congenital HCMV infection may lead to severe fetal disease and possibly mixed HCMV strain infections might have also impact on the clinical consequences for the newborn. Mixed HCMV strain populations were so far detected in saliva but only rarely in urine of congenitally infected newborns. OBJECTIVES: We have therefore analyzed the extent of mixed HCMV genotype populations in urine of congenitally infected newborns using a highly sensitive deep sequencing method. STUDY DESIGN: Twenty urine samples (17 initial and 3 follow-up samples) from 17 congenitally infected newborns with a median HCMV DNA load of 7.5log10 copies/ml were included. Deep sequencing was applied for gO (UL74) genotyping and quantitative real-time PCR assays were used for gB (UL55) and gH (UL75) genotyping. RESULTS: In none of the urine samples a gO genotype mixture was detected, although a mean of 10.000 sequence reads per amplicon was analyzed, which allows to explore gO genotypes down to less than 1% of the total gO sequences. Also only one gB genotype was detected in the patients' initial samples, while a gH genotype mixture was detected in one case using real time PCR with a sensitivity of 5% for minor populations. CONCLUSION: Mixed HCMV genotype populations are only rarely found in urine of congenitally infected newborns even when highly sensitive HCMV genotyping methods are applied.
Asunto(s)
Infecciones por Citomegalovirus/congénito , Citomegalovirus/clasificación , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Orina/virología , Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , ADN Viral/análisis , Genotipo , Humanos , Lactante , Recién Nacido , Filogenia , Análisis de Secuencia de ADN/métodosRESUMEN
BACKGROUND: Cytomegalovirus (CMV) is the most prevalent congenital viral infection and thus places an enormous disease burden on newborn infants. Seroprevalence of maternal antibodies to CMV due to CMV exposure prior to pregnancy is currently the most important protective factor against congenital CMV disease. The aim of this study was to identify potential predictors, and to develop and evaluate a risk-predicting model for the maternal CMV serostatus in early pregnancy. METHODS: Maternal and paternal background information, as well as maternal CMV serostatus in early pregnancy from 882 pregnant women were analyzed. Women were divided into two groups based on their CMV serostatus, and were compared using univariate analysis. To predict serostatus based on epidemiological baseline characteristics, a multiple logistic regression model was calculated using stepwise model selection. Sensitivity and specificity were analyzed using ROC curves. A nomogram based on the model was developed. RESULTS: 646 women were CMV seropositive (73.2%), and 236 were seronegative (26.8%). The groups differed significantly with respect to maternal age (p = 0.006), gravidity (p<0.001), parity (p<0.001), use of assisted reproduction techniques (p = 0.018), maternal and paternal migration background (p<0.001), and maternal and paternal education level (p<0.001). ROC evaluation of the selected prediction model revealed an area under the curve of 0.83 (95%CI: 0.8-0.86), yielding sensitivity and specificity values of 0.69 and 0.86, respectively. CONCLUSION: We identified predictors of maternal CMV serostatus in early pregnancy and developed a risk-predicting model based on baseline epidemiological characteristics. Our findings provide easy accessible information that can influence the counseling of pregnant woman in terms of their CMV-associated risk.
Asunto(s)
Anticuerpos Antivirales/metabolismo , Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/inmunología , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Infecciones por Citomegalovirus/inmunología , Europa (Continente)/epidemiología , Femenino , Humanos , Modelos Logísticos , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Mujeres Embarazadas , Prevalencia , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
BACKGROUND AND AIMS: Monitoring of chronic Hepatitis C (CHC) treatment relies on HCV RNA quantification by means of real-time PCR methods. Assay specific analytical sensitivities may impact therapy management. METHODS: Comparative analysis between three commercial assays (Roche COBAS AmpliPrep/COBAS TaqMan Version 1 (CAP/CTM Ver. 1), Version 2 (CAP/CTM Ver. 2) and the Abbott RealTime HCV (ART) assay) was performed on 247 available samples taken at key decision time points during antiviral therapy of 105 genotype 1 patients (triple therapy: n = 70; dual therapy: n = 35). RESULTS: Overall concordance of HCV RNA measurements was high between the two Roche systems (89%; n = 220/247) but lower between the Roche assays and the ART (CAP/CTM Ver. 1 vs ART: 77.3%; n = 191/247 and CAP/CTM v.2 vs ART: 80.1%; n = 198/247). Most discrepancies were noted in week 4/8 samples with residual viremia (Asunto(s)
Hepatitis C Crónica/sangre
, Monitoreo Fisiológico/instrumentación
, Monitoreo Fisiológico/métodos
, ARN Viral/sangre
, Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación
, Reacción en Cadena en Tiempo Real de la Polimerasa/métodos
, Femenino
, Hepatitis C Crónica/tratamiento farmacológico
, Humanos
, Masculino
RESUMEN
Twenty-one patients aged 4-78 years with influenza A virus-associated acute encephalopathy were studied. Influenza A virus could be detected only in a cerebrospinal fluid (CSF) specimen obtained from 1 of 18 patients, despite the use of a highly sensitive polymerase chain reaction assay. Six patients experienced influenzal encephalopathy during the course of respiratory illness. Five of these patients had hypoprothrombinemia and 4 had increased serum creatinine levels, indicating hepatic and/or renal dysfunction. Fourteen patients experienced postinfluenzal encephalopathy Asunto(s)
Encefalopatías/complicaciones
, Virus de la Influenza A
, Gripe Humana/complicaciones
, Enfermedad Aguda
, Adolescente
, Adulto
, Anciano
, Encefalopatías/virología
, Niño
, Preescolar
, Estudios de Cohortes
, Femenino
, Humanos
, Gripe Humana/virología
, Imagen por Resonancia Magnética
, Masculino
, Persona de Mediana Edad
RESUMEN
During 11 months, all preterm infants admitted to our neonatal care facility with suspected respiratory tract infection were screened for respiratory viruses by polymerase chain reaction. Rhinovirus infection was identified in 16 infants, leading to severe respiratory compromise in most cases. Distribution of rhinovirus infections during the year showed a strong clustering trend, suggesting a major role for nosocomial transmission.
Asunto(s)
Infección Hospitalaria/epidemiología , Recien Nacido Prematuro , Infecciones por Picornaviridae/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Rhinovirus/clasificación , Rhinovirus/aislamiento & purificación , Infección Hospitalaria/virología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Infecciones por Picornaviridae/virología , Reacción en Cadena de la Polimerasa , Infecciones del Sistema Respiratorio/virología , Rhinovirus/genética , Estaciones del Año , Virología/métodosRESUMEN
Patients with malignancies are considered to be at increased risk of acquiring influenza. Because of higher complication and case fatality rates, preventive measures such as vaccination are of great interest. The objective of this study was to assess the acceptability, tolerability and immunogenicity of an adjuvant-free whole-virion pandemic influenza A (H1N1) vaccine in cancer patients with ongoing anticancer treatment during a 'pandemic situation'. Adult patients with hematologic malignancies or solid tumors and concurrent cytotoxic, targeted, and/or hormone therapy were recruited during the influenza A (H1N1) pandemic in 2009/2010 and were offered free vaccine. Antibody titers were measured using virus-specific hemagglutination inhibition assay and ELISA. Among 285 patients with solid tumors who were offered vaccination during their therapy, 260 (91.2%) declined and 25 (8.8%) accepted. Seventeen patients with hematologic malignancies were also vaccinated during therapy; 23 healthy individuals served as a control group. When measured using hemagglutination-inhibition assays, rates of seroprotection, seroconversion, and geometric mean titer ratios after the second vaccination were 96%, 70%, and 4.1 respectively among the healthy individuals, 90%, 52%, and 4.3 among patients with solid tumors, and 67%, 13%, and 1.5 among patients with hematologic malignancies during therapy (P<0.05). When measured using ELISA, seropositivity differed significantly among the three groups after the second vaccination: healthy individuals 74%, patients with solid tumors 57%, those with hematologic malignancies 13% (P<0.001). The vaccine was well tolerated. Our results demonstrate a low uptake of the well tolerated adjuvant-free influenza A (H1N1) vaccine by cancer patients receiving anticancer treatment during the pandemic of 2009/2010. Among the vaccinated patients, the immune response was weaker than that in healthy individuals. The immune response in patients with hematological malignancies was low. Two doses of vaccine are needed in these immunosuppressed patients.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Neoplasias/complicaciones , Adulto , Anciano , Anticuerpos Antivirales/sangre , Antineoplásicos/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Vacunas contra la Influenza/administración & dosificación , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
BACKGROUND: During the influenza pandemic of 2009/10, the whole-virion, Vero-cell-derived, inactivated, pandemic influenza A (H1N1) vaccine Celvapan® (Baxter) was used in Austria. Celvapan® is adjuvant-free and was the only such vaccine at that time in Europe. The objective of this observational, non-interventional, prospective single-center study was to evaluate the immunogenicity and tolerability of two intramuscular doses of this novel vaccine in HIV-positive individuals. METHODS AND FINDINGS: A standard hemagglutination inhibition (HAI) assay was used for evaluation of the seroconversion rate and seroprotection against the pandemic H1N1 strain. In addition, H1N1-specific IgG antibodies were measured using a recently developed ELISA and compared with the HAI results. Tolerability of vaccination was evaluated up to one month after the second dose. A total of 79 HIV-infected adults with an indication for H1N1 vaccination were evaluated. At baseline, 55 of the 79 participants had an HAI titer ≥1:40 and two patients showed a positive IgG ELISA. The seroconversion rate was 31% after the first vaccination, increasing to 41% after the second; the corresponding seroprotection rates were 92% and 83% respectively. ELISA IgG levels were positive in 25% after the first vaccination and in 37% after the second. Among the participants with baseline HAI titers <1:40, 63% seroconverted. Young age was clearly associated with lower HAI titers at baseline and with higher seroconversion rates, whereas none of the seven patients >60 years of age had a baseline HAI titer <1:40 or seroconverted after vaccination. The vaccine was well tolerated. CONCLUSION: The non-adjuvanted pandemic influenza A (H1N1) vaccine was well tolerated and induced a measurable immune response in a sample of HIV-infected individuals.
Asunto(s)
Infecciones por VIH/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Adulto , Femenino , Infecciones por VIH/complicaciones , Pruebas de Inhibición de Hemaglutinación , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/efectos adversos , Gripe Humana/complicaciones , Gripe Humana/inmunología , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: There is a growing need for sensitive high-throughput cytomegalovirus (CMV) PCR tests due to the increasing number of immunocompromised patients requiring monitoring for active CMV infection. OBJECTIVES: To compare the fully automated COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) (CAP/CTM) CMV test (this test is currently under development and not commercially available) for EDTA-plasma to the reference method COBAS(®) AMPLICOR CMV MONITOR. STUDY DESIGN: A prospective feasibility study with parallel analysis of 433 EDTA-plasma samples from 277 patients on both systems was carried out after the analytical performance of the new system had been assessed. RESULTS: The new system has a wide linear range from 2.0 to 7.3 log(10) CMV-DNA copies/ml EDTA-plasma and a detection limit of 46 copies/ml with excellent accuracy and precision. When testing clinical samples, the CAP/CTM CMV test compared extremely well with the COBAS(®) AMPLICOR CMV MONITOR (R(2)=0.93, p<0.001) with increased sensitivity and linear range. Discrepant samples all contained low titers of CMV-DNA. In two of the study patients, CMV-DNAemia was detected by the CAP/CTM CMV test up to eight weeks earlier than by COBAS(®) AMPLICOR CMV MONITOR. CONCLUSION: An IVD/CE marked version of the CAP/CTM CMV test will enable laboratories to provide a sensitive, fully automated high-throughput CMV PCR.