RESUMEN
BACKGROUND: Dengue virus (DENV) is estimated to infect 390 million people annually. However, few host factors that alter disease severity are known. Malnutrition, defined as both over- and undernutrition, is a growing problem worldwide and has long been linked to dengue disease severity by epidemiological and anecdotal observations. Accordingly, we sought to establish a mouse model to assess the impact of nutritional status on DENV disease severity. RESULTS: Using transiently immunocompromised mice, we established a model of mild dengue disease with measurable viremia. We then applied it to study the effects of healthy weight, obese, and low-protein diets representing normal, over-, and undernutrition, respectively. Upon infection with DENV serotype 2, obese mice experienced more severe morbidity in the form of weight loss and thrombocytopenia compared to healthy weight groups. Additionally, obesity altered cytokine expression following DENV infection. Although low protein-fed mice did not lose significant weight after DENV2 infection, they also experienced a reduction in platelets as well as increased spleen pathology and viral titers. CONCLUSIONS: Our results indicate that obese or undernourished mice incur greater disease severity after DENV infection. These studies establish a role for nutritional status in DENV disease severity.
Asunto(s)
Peso Corporal/fisiología , Dengue/virología , Dieta Alta en Grasa/efectos adversos , Dieta con Restricción de Proteínas/efectos adversos , Estado Nutricional , Animales , Dengue/fisiopatología , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Viremia/fisiopatologíaRESUMEN
We noted a recent increase in number of immunocompromised children with CMV viremia at our institution. The purpose of this study was to determine the frequency of CMV viremia in this population and evaluate factors associated with drug-resistant mutations. A retrospective review of immunocompromised hosts, 0-21 years of age, who had CMV viremia during 2007-2017. CMV viremia was detected using PCR assays. Genetic mutation assays were performed using PCR sequencing of the phosophotransferase UL 97 gene and the polymerase UL54 gene of CMV using Quest Diagnostics (San Juan Capistrano, CA, USA) or ARUP Labs (Salt Lake City, UT, USA). Thirty-one patients were identified, including 10 (32%) during the last 2 years. Of the 31 patients, 18 had hematopoietic stem cell transplantation (HSCT), 5 had primary immunodeficiency, 4 had malignancies, 3 had heart transplantation and 1 had new Human Immunodeficiency virus (HIV) infection. Antiviral resistance testing was performed on isolates from seven patients: five with persistent viremia (>1 mo), and two prior to starting antiviral therapy. Resistance was identified in three patients' isolates: two with common variable immunodeficiency (CVID) and one with recurrent Hodgkin's lymphoma who had undergone autologous HSCT. The two patients with CVID had chronic diarrhea and malabsorption and had received prolonged oral valganciclovir courses prior to emergence of resistance. The patient with Hodgkin's lymphoma had received a prolonged IV ganciclovir course. All three tested positive for UL97 mutation and two had both UL97 and UL54 gene mutations. Majority of our patients (21/31) with CMV viremia were transplant recipients and ganciclovir resistance developed in 10%. Two had intestinal malabsorption. Treatment with oral valganciclovir should be avoided in patients with poor gut absorption as that may increase the risk of resistance.
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Citomegalovirus/patogenicidad , Viremia/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVES: The clinical significance of low-level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV-positive adults in relation to LLV or permanent virological suppression during long-term ART. METHODS: Plasma levels of C-reactive protein (CRP), D-dimer, vascular cell adhesion molecule 1 (VCAM-1), suppression of tumorigenicity 2 (ST2), growth differentiation factor 15 (GDF-15), soluble CD14 (sCD14), soluble CD163 (sCD163), interferon-γ-induced protein 10 (IP-10) and ß-2-microglobulin were measured in 34 individuals with LLV (viral load 50-999 HIV-1 RNA copies/mL) and in matched controls with persistent virological suppression. Biomarker levels were analysed in samples obtained during episodes of LLV and follow-up samples obtained 1 year later (with similar timing for controls). All biomarkers were analysed using an independent sample t-test and analysis of covariance (ANCOVA) after logarithmic transformation. Log-rank analysis was applied for markers with concentration values out of range. RESULTS: Compared with controls, patients with LLV had significantly higher levels of GDF-15 [geometric mean 3416 (95% confidence interval (CI) 804-14 516) pg/mL versus 2002 (95% CI 355-11 295) pg/mL in controls; P = 0.026] and D-dimer [mean 1114 (95% CI 125-9917) ng/mL versus 756 (95% CI 157-3626) ng/mL; P = 0.038] after adjustment for age, CD4 count nadir and type of ART. In the unadjusted t-test, only GDF-15 was significantly higher and in the log-rank test, both GDF-15 and D-dimer were significantly elevated. No significant differences were observed for the other biomarkers analysed. CONCLUSIONS: Although levels of inflammation markers were similar in ART recipients with and without LLV, persons with LLV had significantly higher levels of GDF-15 and D-dimer. These findings suggest a potential link between LLV and cardiovascular outcomes.
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Coagulación Sanguínea/inmunología , Enfermedades Cardiovasculares/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Viremia/inmunología , Adulto , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Recuento de Linfocito CD4 , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/virología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Proteínas Ligadas a GPI/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Infecciones por VIH/sangre , Infecciones por VIH/fisiopatología , Humanos , Receptores de Lipopolisacáridos/sangre , Masculino , Receptores de IgG/sangre , Estudios Retrospectivos , Molécula 1 de Adhesión Celular Vascular/sangre , Carga Viral , Viremia/fisiopatologíaRESUMEN
Human herpes virus-6 (HHV-6) and human herpes virus-7 (HHV-7) are immunomodulating viruses potentially affecting the nervous system. We evaluated the influence of HHV-6 and HHV-7 infections on fibromyalgia (FM) clinical course. Forty-three FM patients and 50 control group participants were enrolled. 39.50% (n = 17) FM patients had light A delta and C nerve fiber damage, 27.91% (n = 12) had severe A delta and C nerve fiber damage. 67.44% (n = 29) FM patients had loss of warm sensation in feet, loss of heat pain sensation, and increased cold pain sensation (34.90%, n = 15 in both findings). HHV-6 and HHV-7 genomic sequences in peripheral blood DNA in 23/43 (51.00%) and 34/43 (75.50%) of samples from FM patients and in 3/50 (6.00%) and 26/50 (52.00%) of samples from the control group individuals were detected. Active HHV-6 (plasma viremia) or HHV-7 infection was revealed only in FM patients (4/23, 17.40% and 4/34, 11.80%, respectively). A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). 23/43 patients from the FM group and control group participants HHV-6 and 34/45 HHV-7 did have infection markers. A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). No difference was found between detection frequency of persistent HHV-6 and HHV-7 infection between FM patients and the control group. Statistically significant correlation was observed between quantitation of changes in QST thermal modalities and HHV-6 infection. There was no correlation between A delta and C nerve fiber damage and HHV-7 infection.
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Fibromialgia/diagnóstico , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Dolor/diagnóstico , Infecciones por Roseolovirus/diagnóstico , Viremia/diagnóstico , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Fibromialgia/complicaciones , Fibromialgia/fisiopatología , Fibromialgia/virología , Herpesvirus Humano 6/crecimiento & desarrollo , Herpesvirus Humano 6/patogenicidad , Herpesvirus Humano 7/crecimiento & desarrollo , Herpesvirus Humano 7/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Dolor/complicaciones , Dolor/fisiopatología , Dolor/virología , Dimensión del Dolor , Infecciones por Roseolovirus/complicaciones , Infecciones por Roseolovirus/fisiopatología , Infecciones por Roseolovirus/virología , Índice de Severidad de la Enfermedad , Carga Viral/genética , Viremia/complicaciones , Viremia/fisiopatología , Viremia/virologíaRESUMEN
Discovered in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV) has been associated with four human malignancies including Kaposi's sarcoma, primary effusion lymphoma, a subset of multicentric Castleman's disease, and KSHV inflammatory cytokine syndrome. These malignancies mostly occur in immunocompromised patients including patients with acquired immunodeficiency syndrome and often cause significant mortality because of the lack of effective therapies. Significant progresses have been made to understand the molecular basis of KSHV infection and KSHV-induced oncogenesis in the last two decades. This chapter provides an update on the recent advancements focusing on the molecular events of KSHV primary infection, the mechanisms regulating KSHV life cycle, innate and adaptive immunity, mechanism of KSHV-induced tumorigenesis and inflammation, and metabolic reprogramming in KSHV infection and KSHV-transformed cells.
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Síndrome de Inmunodeficiencia Adquirida/virología , Infecciones por Herpesviridae/genética , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/inmunología , Neoplasias/virología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Carcinogénesis/genética , Carcinogénesis/inmunología , Enfermedad de Castleman/fisiopatología , Enfermedad de Castleman/virología , Coinfección/virología , Citocinas/inmunología , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/fisiología , Humanos , Huésped Inmunocomprometido , Inflamación/inmunología , Inflamación/fisiopatología , Inflamación/virología , Linfoma de Efusión Primaria/fisiopatología , Linfoma de Efusión Primaria/virología , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/fisiopatología , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/virología , Síndrome , Viremia/inmunología , Viremia/fisiopatología , Viremia/virologíaRESUMEN
Although viral replication is apparently controlled with highly active antiretroviral therapy, cardiovascular risk of patients living with HIV remains a concern in clinical practice with population ageing. Cardiovascular risk profile in patients living with HIV is changing with the emergence of new parameters related to the persistence of residual viral replication, the antecedent and severity of immunodepression, the resulting chronic inflammation, as well as prolonged exposure to antiretroviral drugs and "classical" cardiovascular risk factors. Estimating risk models in patients living with HIV are not sufficient to integrate duration of exposure and control quality of all cardiovascular risk factors at the individual level. Aortic stiffness is a marker of the alteration of structural and functional properties of the wall of the large arterial trunks. This marker has an independent predictive value for total and cardiovascular mortality in the general population but also in the presence of risk factors and may offer clinical information about accelerated vascular ageing in people living with HIV. Aortic stiffness can be estimated non-invasively by applanation tonometry with carotid-femoral pulse wave velocity. This measure may be useful in clinical practice for early identification of at risk patients. Study of the determinants of aortic stiffening process in this population may optimize cardiovascular prevention.
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Enfermedades Cardiovasculares/epidemiología , Infecciones por VIH/fisiopatología , Hemodinámica , Rigidez Vascular , Envejecimiento , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Enfermedades Cardiovasculares/etiología , Comorbilidad , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Enfermedades Renales/etiología , Enfermedades Renales/fisiopatología , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/fisiopatología , Análisis de la Onda del Pulso , Medición de Riesgo , Factores de Riesgo , Carga Viral , Viremia/tratamiento farmacológico , Viremia/fisiopatologíaRESUMEN
PURPOSE: The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4+, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally. METHODS: This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015. RESULTS: Of the 146 participants (mean age 52 ± 10 years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4+ <200 cells/µl was associated with significant diffusion impairment compared to CD4+ ≥200 cells/µl (DLCO 56 vs. 70%, p = <0.01). VL (viral load) ≥75 copies/ml was associated with significant diffusion impairment compared to VL <75 copies/ml (DLCO 60 vs. 71%, p = <0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4+ and VL correlated with DLCO (r = +0.33; p = <0.01; r = -0.26; p = <0.01) and no correlation was noted with FEV1, FEV1/FVC, or TLC. Current smoking and history of AIDS correlated with DLCO (r = -0.20; p = 0.03; r = -0.20; p = 0.04). After adjusting for smoking and other confounders, VL ≥75 copies/ml correlated with a 11.2 (CI 95% [3.03-19.4], p = <0.01) decrease in DLCO. In Spearman's Rank correlation, there was a negative correlation between change in VL and change in DLCO over time (ρ = -0.47; p = <0.01). CONCLUSION: The presence of viremia in individuals with HIV is independently associated with impaired DLCO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.
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Recuento de Linfocito CD4 , Infecciones por VIH/fisiopatología , Pulmón/fisiopatología , Fumar/fisiopatología , Carga Viral , Viremia/fisiopatología , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Monóxido de Carbono , Femenino , Volumen Espiratorio Forzado , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Capacidad de Difusión Pulmonar , Pruebas de Función Respiratoria , Estudios Retrospectivos , Fumar/epidemiología , Capacidad Pulmonar Total , Viremia/epidemiología , Capacidad VitalRESUMEN
BACKGROUND: Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) cocirculate in Nicaragua. In this study, we sought to compare the quantified viremia and clinical presentation of patients infected with 1 or more of these viruses. METHODS: Acute-phase serum samples from 346 patients with a suspected arboviral illness were tested using a multiplex real-time reverse-transcription polymerase chain reaction for ZIKV, CHIKV, and DENV. Viremia was quantitated for each detected virus, and clinical information from request forms submitted with each sample was recorded. RESULTS: A total of 263 patients tested positive for 1 or more viruses: 192 patients tested positive for a single virus (monoinfections) and 71 patients tested positive for 2 or all 3 viruses (coinfections). Quantifiable viremia was lower in ZIKV infections compared with CHIKV or DENV (mean 4.70 vs 6.42 and 5.84 log10 copies/mL serum, respectively; P < .001 for both comparisons), and for each virus, mean viremia was significantly lower in coinfections than in monoinfections. Compared with patients with CHIKV or DENV, ZIKV patients were more likely to have a rash (P < .001) and less likely to be febrile (P < .05) or require hospitalization (P < .001). Among all patients, hospitalized cases had higher viremia than those who did not require hospitalization (7.1 vs 4.1 log10 copies/mL serum, respectively; P < .001). CONCLUSIONS: ZIKV, CHIKV, and DENV result in similar clinical presentations, and coinfections may be relatively common. Our findings illustrate the need for accurate, multiplex diagnostics for patient care and epidemiologic surveillance.
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Fiebre Chikungunya/virología , Dengue/virología , Viremia , Infección por el Virus Zika/virología , Adulto , Fiebre Chikungunya/complicaciones , Fiebre Chikungunya/fisiopatología , Coinfección , Dengue/complicaciones , Dengue/fisiopatología , Femenino , Humanos , Masculino , Nicaragua , Viremia/fisiopatología , Viremia/virología , Adulto Joven , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/fisiopatologíaRESUMEN
Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) was first characterized in 2006 in China, and it causes great economic losses to the Chinese swine production industry. A China Landrace pig, the Tibetan pig, which has striking phenotypic and physiological differences from lowland pigs, is mainly distributed in the Tibetan highlands of China. The susceptibility of the Tibetan pig to HP-PRRSV has not been reported. In this study, 15 4-week-old Tibetan piglets were divided into three groups, and their susceptibility to HP-PRRSV was examined in the highland region. Five pigs in group 1 were inoculated intranasally with HP-PRRSV strain BB0907. At 2days post-inoculation, five other pigs were introduced into this group and then removed to a separated room to serve as contact group 2. Meanwhile, five pigs in group 3 were mock infected and used as controls. The results showed that the pigs in the inoculated and contact groups showed high fevers and clear clinical signs, including depression, anorexia, lethargy, sticky eye secretions, and hind limb paralysis, with high mortality. The main symptom was interstitial pneumonia. Viremia appeared on days 4 to 14 post-infection. HP-PRRSV infection resulted in inflammatory responses within the first week of infection, as evidenced by the expression of tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6, and IL-10. All the data indicate that the Tibetan pig is susceptible to HP-PRRSV infection. Thus, it is necessary to investigate and prevent PRRSV infections in the highland region in China.
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Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Enfermedades de los Porcinos/virología , Administración Intranasal/veterinaria , Animales , Síndrome Respiratorio y de la Reproducción Porcina/fisiopatología , Porcinos , Enfermedades de los Porcinos/fisiopatología , Tibet , Viremia/fisiopatología , Viremia/veterinaria , Viremia/virologíaRESUMEN
Spring viraemia of carp virus (SVCV) is the causative pathogen of the outbreaks of an acute haemorrhagic and contagious viraemia responsible for the significant mortality in several cyprinid species. However, the endocytic pathway(s) and their regulatory molecules have not been characterized for SVCV. Here, using a combination of specific pharmacological inhibitors, transmission electron microscopy, immunofluorescence microscopy and real-time quantitative PCR, we found that SVCV entered grass carp ovary cells via clathrin-mediated endocytosis and macropinocytosis in a low-pH-dependent manner. We also discovered that dynamin II, actin microfilaments and microtubules were essential for SVCV internalization. Moreover, we found that the P21-activated kinase 1 inhibitor IPA-3 and the protein kinase C inhibitor rottlerin could block SVCV cell entry and replication, while phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 could promote SVCV infection. Results presented in this study provide helpful insight into revealing the initial steps of SVCV infection, and they may facilitate the development of therapeutic interventions.
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Carpas/virología , Clatrina/metabolismo , Endocitosis , Enfermedades de los Peces/virología , Proteínas de Peces/metabolismo , Ovario/virología , Vesiculovirus/fisiología , Viremia/veterinaria , Animales , Femenino , Enfermedades de los Peces/metabolismo , Enfermedades de los Peces/fisiopatología , Viremia/metabolismo , Viremia/fisiopatología , Viremia/virología , Internalización del VirusRESUMEN
Successful treatment of HIV infection requires regular clinical follow-up. A previously published risk-prediction tool (RPT) utilizing data from the electronic health record (EHR) including medication adherence, previous appointment attendance, substance abuse, recent CD4+ count, prior antiretroviral therapy (ART) exposure, prior treatment failure, and recent HIV-1 viral load (VL) has been shown to predict virologic failure at 1 year. If this same tool could be used to predict the more immediate event of appointment attendance, high-risk patients could be identified and interventions could be targeted to improve this outcome. We conducted an observational cohort study at the Vanderbilt Comprehensive Care Clinic from August 2013 through March 2014. Patients with routine medical appointments and most recent HIV-1 VL >200 copies/mL were included. Risk scores for a modified RPT were calculated based on data from the EHR. Odds ratios (OR) for missing the next appointment were estimated using multivariable logistic regression. Among 510 persons included, median age was 39 years, 74% were male, 55% were black, median CD4+ count was 327 cells/mm(3) [Interquartile Range (IQR): 142-560], and median HIV-1 VL was 21,818 copies/mL (IQR: 2,030-69,597). Medium [OR 3.95, 95% confidence interval (CI) 2.08-7.50, p-value<0.01] and high (OR 9.55, 95% CI 4.31-21.16, p-value<0.01) vs. low RPT risk scores were independently associated with missing the next appointment. RPT scores, constructed using readily available data, allow for risk-stratification of HIV medical appointment non-attendance and could support targeting limited resources to improve appointment adherence in groups most at-risk of poor HIV outcomes.
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Fármacos Anti-VIH/administración & dosificación , Citas y Horarios , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Aceptación de la Atención de Salud , Viremia/fisiopatología , Adulto , Enfermedad Crónica , Estudios de Cohortes , VIH-1/efectos de los fármacos , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Riesgo , Insuficiencia del Tratamiento , Carga Viral , Viremia/tratamiento farmacológicoRESUMEN
The significance of BK viruria and viremia in non-renal solid organ transplants is poorly understood. A systematic review was performed reviewing the incidence and implications of BK virus replication in non-renal solid organ transplants. Ninety-seven studies were identified, of which 18 including lung, heart, liver and pancreas transplants were included. The overall incidence of BK viruria and viremia was 20% and 3% respectively and 17 cases of BK nephropathy were identified. Heart transplant recipients had a higher overall incidence of BK viremia than other non-renal organ types, and the majority of cases of BK virus-associated nephropathy were in heart transplant recipients. The incidence of BK viremia was significantly lower in non-renal solid organ transplants than that of renal transplant recipients and BK virus-associated nephropathy was rare. BK virus-associated nephropathy may be considered in heart transplant recipients who have unexplained and persistent renal dysfunction not attributable to other causes.
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Virus BK/aislamiento & purificación , Trasplante de Órganos/efectos adversos , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/etiología , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/etiología , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Masculino , Trasplante de Órganos/métodos , Infecciones por Polyomavirus/fisiopatología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Prevalencia , Pronóstico , Medición de Riesgo , Infecciones Tumorales por Virus/fisiopatología , Viremia/epidemiología , Viremia/etiología , Viremia/fisiopatología , Replicación ViralRESUMEN
BACKGROUND: Herpes zoster (HZ) in patients receiving tumor necrosis factor (TNF) antagonists may be more severe and the incidence seems increased. The influence of TNF antagonists on varicella zoster virus (VZV) reactivation is unknown. OBJECTIVE: To prospectively search in a pilot study for VZV DNA in sequential blood samples before and after infliximab administration. SETTING: University medical center. SUBJECTS AND METHODS: Blood samples of six patients with longstanding and severe plaque psoriasis were taken on day 1 (before infliximab administration) and on days 2, 7, 21 and 42 for the determination of VZV viremia by ORF21 real-time polymerase chain reaction. Patients with varicella, HZ and normal subjects were included as controls. RESULTS: None of the six patients presented VZV viremia at any of the time points. High-load viremia was present during varicella, low-load viremia in some HZ patients and no viremia in the control patients. LIMITATIONS: Small number of patients. CONCLUSIONS: In this pilot study, infliximab did not reactivate VZV and did not induce subclinical VZV viremia.
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Anticuerpos Monoclonales/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3/fisiología , Psoriasis/tratamiento farmacológico , Activación Viral/efectos de los fármacos , Anciano , Anticuerpos Monoclonales/farmacología , Fármacos Dermatológicos/farmacología , Femenino , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Proyectos Piloto , Carga Viral , Viremia/fisiopatologíaRESUMEN
In vivo T-cell depletion, using alemtuzumab therapy prior to SCT, can reduce the incidence of GVHD. This treatment has a potential to delay immune reconstitution resulting in increased morbidity due to viral illnesses. We retrospectively analyzed data on all pediatric patients with non-malignant disorders who received alemtuzumab-based conditioning regimens in our center over the last 10 yr (n = 91). Our data show an OS of 91.2%. The incidence of acute (grade 2-4) GVHD was 18.7% and that of chronic GVHD 5.5%. Viremia due to adenovirus, EBV and CMV was seen in 19.8%, 64.8% and 39.6% patients, respectively, with only two deaths attributed to viral infection (adenovirus). Chimerism level at three month was predictive of graft outcome. Nine patients, who had graft failure after first SCT, were salvaged with a second SCT using RIC and same donor (if available). Based on these results, we conclude that the use of in vivo T-cell depletion is safe, achieves good chimerism and does not lead to increased morbidity and mortality due to viral infections. It is associated with a reduced incidence of chronic GVHD.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfocitos T/inmunología , Adenoviridae/metabolismo , Adolescente , Alemtuzumab , Anemia Aplásica/terapia , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Lactante , Masculino , Enfermedades Metabólicas/terapia , Estudios Retrospectivos , Quimera por Trasplante , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Donante no Emparentado , Viremia/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne pathogen that can cause fatal severe fever with thrombocytopenia syndrome, was first identified in China in 2009. Limited evidence suggests that SFTSV can be transmitted between humans via blood contact, raising concerns over transfusion safety. A study of donor samples from three Chinese blood centers was conducted to investigate the seroprevalence and rate of SFTSV viremia among Chinese blood donors. STUDY DESIGN AND METHODS: From April 16 to October 31, 2012, a total of 17,208 plasma samples were collected from donors at Xinyang (located in an SFTSV-endemic area), Mianyang, and Luoyang Blood Centers. Assessment of anti-SFTSV total antibody was performed on all samples using enzyme-linked immunosorbent assay. Repeat-reactive samples were tested for SFTSV RNA using reverse transcription (RT)-real-time polymerase chain reaction (PCR) assay with Taqman probes. In addition, 9960 of the Xinyang samples were tested in pools of 4 by the same PCR method and each of the samples in a reactive pool was tested individually. RESULTS: Donor seroreactivity rates were as follows: Xinyang, 0.54% (80/14,752); Mianyang, 0.27% (3/1130); and Luoyang, 0.28% (3/1326). All seroreactive samples were negative on RT-PCR single-sample testing. Two RT-PCR-reactive donor samples were identified, both with estimated viral load of less than 20 plaque-forming units/mL. The RNA prevalence rate for SFTSV among donors in Xinyang was 0.02%. CONCLUSION: This was the first multiregion study of SFTSV sero- and viral prevalence among Chinese blood donors. Viral prevalence was low and no seroreactive sample was viremic, suggesting a limited impact of SFTSV on blood safety in China.
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Viremia/epidemiología , Adolescente , Adulto , Donantes de Sangre , China , Ensayo de Inmunoadsorción Enzimática , Femenino , Fiebre/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Seroepidemiológicos , Trombocitopenia/epidemiología , Trombocitopenia/fisiopatología , Viremia/sangre , Viremia/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: While residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences. METHODS: This cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL <20 copies/mL for ≥1 year). Residual HIV-VL was measured using an ultrasensitive assay (quantification limit: 1 copy/ml). Patients were categorized as having detectable (D; 1-20 copies/mL, nâ=â14) or undetectable (UD; <1 copies/mL, nâ=â33) HIV-VL. Linear regression was used to model the difference in total carotid intima-media thickness [c-IMT, measures averaged across common carotid artery (cca), bifurcation, and internal carotid artery] and cca-IMT alone across detection groups. Multivariable models were constructed for each endpoint in a forward-stepwise approach. RESULTS: No significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQRâ=â6.8-10.9), nadir CD4+T-cell (208/mm3, IQRâ=â143-378), and CD4+T-cell count (555/mm3, IQRâ=â458-707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (pâ=â0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, pâ=â0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (pâ=â0.2), however there was large variability in bifurcation c-IMT measurements. CONCLUSIONS: Higher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis.
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Antirretrovirales/administración & dosificación , Arteria Carótida Común , Grosor Intima-Media Carotídeo , Infecciones por VIH , VIH-1 , Viremia , Adulto , Aterosclerosis/sangre , Aterosclerosis/patología , Aterosclerosis/fisiopatología , Arteria Carótida Común/patología , Arteria Carótida Común/fisiopatología , Estudios Transversales , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Infecciones por VIH/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Viremia/tratamiento farmacológico , Viremia/patología , Viremia/fisiopatologíaRESUMEN
West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry have been proposed for WNV neuroinvasion, which revolve mainly around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal transport, respectively. However, an overrepresentation of in vitro studies without adequate in vivo validation continues to obscure our understanding of the mechanism(s). Furthermore, WNV infection in the current rodent models does not generate a similar viremia and character of CNS infection, as seen in the common target hosts, humans and horses. These differences ultimately question the applicability of rodent models for pathogenesis investigations. Finally, the role of several barriers against CNS insults, such as the blood-cerebrospinal fluid (CSF), the CSF-brain and the blood-spinal cord barriers, remain largely unexplored, highlighting the infancy of this field. In this review, a systematic and critical appraisal of the current evidence relevant to the possible mechanism(s) of WNV neuroinvasion is conducted.
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Encefalitis Viral/virología , Regulación Viral de la Expresión Génica , Proteínas Virales/genética , Viremia/virología , Internalización del Virus , Virus del Nilo Occidental/metabolismo , Uniones Adherentes/metabolismo , Uniones Adherentes/virología , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/virología , Barrera Hematonerviosa/metabolismo , Barrera Hematonerviosa/virología , Encéfalo/patología , Encéfalo/virología , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Encefalitis Viral/fisiopatología , Caballos , Humanos , Médula Espinal/patología , Médula Espinal/virología , Uniones Estrechas/metabolismo , Uniones Estrechas/virología , Proteínas Virales/metabolismo , Viremia/fisiopatología , Virus del Nilo Occidental/genética , Virus del Nilo Occidental/patogenicidadRESUMEN
The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases.
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Modelos Animales de Enfermedad , Síndrome Pulmonar por Hantavirus/fisiopatología , Macaca mulatta/virología , Enfermedades de los Monos/virología , Peromyscus/virología , Virus Sin Nombre/genética , Animales , Chlorocebus aethiops , Síndrome Pulmonar por Hantavirus/diagnóstico por imagen , Síndrome Pulmonar por Hantavirus/transmisión , Pulmón/diagnóstico por imagen , Pulmón/virología , Datos de Secuencia Molecular , Enfermedades de los Monos/fisiopatología , Enfermedades de los Monos/transmisión , América del Norte , ARN Viral/genética , Radiografía , Células Vero , Viremia/fisiopatologíaRESUMEN
BACKGROUND: Serum creatinine and cystatin C are used as markers of glomerular filtration rate (GFR). The performance of these GFR markers relative to exogenously measured GFR (mGFR) in HIV-positive individuals is not well established. METHODS: We assessed the performance of the chronic kidney disease epidemiology collaboration equations based on serum concentrations of creatinine (eGFRcr), cystatin C (eGFRcys) and both biomarkers combined (eGFRcr-cys) in 187 HIV-positive and 98 HIV-negative participants. Measured GFR was calculated by plasma iohexol clearance. Bias and accuracy were defined as the difference between eGFR and mGFR and the percentage of eGFR observations within 30% of mGFR, respectively. Activated CD4 and CD8 T-cells (CD38+ HLA-DR+) were measured by flow cytometry. RESULTS: The median mGFR was >100 ml/min/1.73 m(2) in both groups. All equations tended to be less accurate in HIV-positive than in HIV-negative subjects, with eGFRcr-cys being the most accurate overall. In the HIV-positive group, eGFRcys was significantly less accurate and more biased than eGFRcr and eGFRcr_cys. Additionally eGFRcys bias and accuracy were strongly associated with use of antiretroviral therapy, HIV RNA suppression, and percentages of activated CD4 or CD8 T-cells. Hepatitis C seropositivity was associated with larger eGFRcys bias in both HIV-positive and HIV-negative groups. In contrast, eGFRcr accuracy and bias were not associated with HIV-related factors, T-cell activation, or hepatitis C. CONCLUSIONS: The performance of eGFRcys relative to mGFR was strongly correlated with HIV treatment factors and markers of T-cell activation, which may limit its usefulness as a GFR marker in this population.
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Linfocitos T CD8-positivos/inmunología , Creatinina/sangre , Cistatina C/sangre , Tasa de Filtración Glomerular , Infecciones por VIH/inmunología , Activación de Linfocitos/inmunología , Viremia/inmunología , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/inmunología , Insuficiencia Renal Crónica/fisiopatología , Viremia/sangre , Viremia/fisiopatologíaRESUMEN
The mechanisms by which a small percentage of HIV-1 infected individuals known as elite suppressors or controllers are able to control viral replication are not fully understood. Early cases of viremic control were attributed to infection with defective virus, but subsequent work has demonstrated that infection with a defective virus is not the exclusive cause of control. Replication-competent virus has been isolated from patients who control viral replication, and studies have demonstrated that evolution occurs in plasma virus but not in virus isolates from the latent reservoir. Additionally, transmission pair studies have demonstrated that patients infected with similar viruses can have dramatically different outcomes of infection. An increased understanding of the viral factors associated with control is important to understand the interplay between viral replication and host control, and has implications for the design of an effective therapeutic vaccine that can lead to a functional cure of HIV-1 infection.