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1.
J Med Virol ; 96(8): e29836, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39078052

RESUMEN

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow-Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations.


Asunto(s)
Herpesvirus Humano 4 , Herpesvirus Humano 8 , Hibridación Fluorescente in Situ , Linfoma de Efusión Primaria , Humanos , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/aislamiento & purificación , Hibridación Fluorescente in Situ/métodos , Linfoma de Efusión Primaria/virología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Masculino , Anciano , Persona de Mediana Edad , Femenino , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Anciano de 80 o más Años
2.
Virol J ; 21(1): 78, 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566231

RESUMEN

Chronic obstructive pulmonary disease (COPD) affects over 250 million individuals globally and stands as the third leading cause of mortality. Respiratory viral infections serve as the primary drivers of acute exacerbations, hastening the decline in lung function and worsening the prognosis. Notably, Human Parainfluenza Virus type 3 (HPIV-3) is responsible for COPD exacerbations with a frequency comparable to that of Respiratory Syncytial Virus and Influenza viruses. However, the impact of HPIV-3 on respiratory epithelium within the context of COPD remains uncharacterized.In this study, we employed in vitro reconstitution of lower airway epithelia from lung tissues sourced from healthy donors (n = 4) and COPD patients (n = 5), maintained under air-liquid interface conditions. Through a next-generation sequencing-based transcriptome analysis, we compared the cellular response to HPIV-3 infection.Prior to infection, COPD respiratory epithelia exhibited a pro-inflammatory profile, notably enriched in canonical pathways linked to antiviral response, B cell signaling, IL-17 signaling, and epithelial-mesenchymal transition, in contrast to non-COPD epithelia. Intriguingly, post HPIV-3 infection, only non-COPD epithelia exhibited significant enrichment in interferon signaling, pattern recognition receptors of viruses and bacteria, and other pathways involved in antiviral responses. This deficiency could potentially hinder immune cell recruitment essential for controlling viral infections, thus fostering prolonged viral presence and persistent inflammation.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Virus Sincitial Respiratorio Humano , Virosis , Virus , Humanos , Virus de la Parainfluenza 3 Humana , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Epitelio , Antivirales/uso terapéutico
3.
PLoS Med ; 20(12): e1004317, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38060611

RESUMEN

BACKGROUND: Asymptomatic and paucisymptomatic infections account for a substantial portion of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions. The value of intensified screening strategies, especially in emergency departments (EDs), in reaching asymptomatic and paucisymptomatic patients and helping to improve detection and reduce transmission has not been documented. The objective of this study was to evaluate in EDs whether an intensified SARS-CoV-2 screening strategy combining nurse-driven screening for asymptomatic/paucisymptomatic patients with routine practice (intervention) could contribute to higher detection of SARS-CoV-2 infections compared to routine practice alone, including screening for symptomatic or hospitalized patients (control). METHODS AND FINDINGS: We conducted a cluster-randomized, two-period, crossover trial from February 2021 to May 2021 in 18 EDs in the Paris metropolitan area, France. All adults visiting the EDs were eligible. At the start of the first period, 18 EDs were randomized to the intervention or control strategy by balanced block randomization with stratification, with the alternative condition being applied in the second period. During the control period, routine screening for SARS-CoV-2 included screening for symptomatic or hospitalized patients. During the intervention period, in addition to routine screening practice, a questionnaire about risk exposure and symptoms and a SARS-CoV-2 screening test were offered by nurses to all remaining asymptomatic/paucisymptomatic patients. The primary outcome was the proportion of newly diagnosed SARS-CoV-2-positive patients among all adults visiting the 18 EDs. Primary analysis was by intention-to-treat. The primary outcome was analyzed using a generalized linear mixed model (Poisson distribution) with the center and center by period as random effects and the strategy (intervention versus control) and period (modeled as a weekly categorical variable) as fixed effects with additional adjustment for community incidence. During the intervention and control periods, 69,248 patients and 69,104 patients, respectively, were included for a total of 138,352 patients. Patients had a median age of 45.0 years [31.0, 63.0], and women represented 45.7% of the patients. During the intervention period, 6,332 asymptomatic/paucisymptomatic patients completed the questionnaire; 4,283 were screened for SARS-CoV-2 by nurses, leading to 224 new SARS-CoV-2 diagnoses. A total of 1,859 patients versus 2,084 patients were newly diagnosed during the intervention and control periods, respectively (adjusted analysis: 26.7/1,000 versus 26.2/1,000, adjusted relative risk: 1.02 (95% confidence interval (CI) [0.94, 1.11]; p = 0.634)). The main limitation of this study is that it was conducted in a rapidly evolving epidemiological context. CONCLUSIONS: The results of this study showed that intensified screening for SARS-CoV-2 in EDs was unlikely to identify a higher proportion of newly diagnosed patients. TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov NCT04756609.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Femenino , Humanos , Persona de Mediana Edad , COVID-19/diagnóstico , COVID-19/epidemiología , Estudios Cruzados , Servicio de Urgencia en Hospital , Francia/epidemiología , Paris/epidemiología , Encuestas y Cuestionarios , Masculino
4.
J Med Virol ; 95(12): e29319, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38102899

RESUMEN

Accurate prediction of COVID-19 severity remains a challenge. Torque teno virus (TTV), recognized as a surrogate marker of functional immunity in solid organ transplant recipients, holds the potential for assessing infection outcomes. We investigated whether quantifying TTV in nasopharyngeal samples upon emergency department (ED) admission could serve as an early predictor of COVID-19 severity. Retrospective single-center study in the ED of Saint-Louis Hospital in Paris, France. TTV DNA was quantified in nasopharyngeal swab samples collected for SARS-CoV-2 testing. Among 295 SARS-CoV-2 infected patients, 92 returned home, 160 were admitted to medical wards, and 43 to the intensive care unit (ICU). Elevated TTV loads were observed in ICU patients (median: 3.02 log copies/mL, interquartile range [IQR]: 2.215-3.825), exceeding those in discharged (2.215, [0; 2.962]) or hospitalized patients (2.24, [0; 3.29]) (p = 0.006). Multivariate analysis identified diabetes, obesity, hepatitis, fever, dyspnea, oxygen requirement, and TTV load as predictors of ICU admission. A 2.91 log10 copies/mL TTV threshold independently predicted ICU admission. Nasopharyngeal TTV quantification in SARS-CoV-2 infected patients is linked to the likelihood of ICU admission and might reflect respiratory immunosuppression.


Asunto(s)
COVID-19 , Infecciones por Virus ADN , Torque teno virus , Humanos , Torque teno virus/genética , SARS-CoV-2/genética , Estudios Retrospectivos , Prueba de COVID-19 , COVID-19/diagnóstico , ADN Viral , Unidades de Cuidados Intensivos , Carga Viral
5.
Transpl Infect Dis ; 25(5): e14118, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37594199

RESUMEN

BACKGROUND: Human parvovirus B19 (B19V) infection is associated with pure red cell aplasia (PRCA) in immunocompromised patients; however, the spectrum of manifestations associated with B19V in allogeneic hematopoietic stem cell transplantation recipients (alloHSCT) has rarely been reported. METHODS: In this study, we aimed to report clinical and immune features of B19V infection after alloHSCT. We retrospectively collected and analyzed clinical and microbiological data of all transplanted patients with B19V DNAmia or tissue infection detected by polymerase chain reaction (PCR) in our center from 2010 to 2021. RESULTS: We report 35 cases of B19V infections in 33 patients. Median time from transplant to B19V first PCR positivity was 6.9 months (interquartile range (IQR) [1.6-18.9]). No preferential immune profile, type of transplantation or conditioning was identified. Hematological impairment was the most frequent sign, followed by rash and fever. Unconventional clinical forms were also detected, such as acute myelitis and myositis. For some cases, the direct relationship between symptoms and B19V infection was difficult to prove but was suggested by targeted tissue PCR positivity. When hematological impairment was not at the forefront, reticulocytopenia helped to diagnose B19V infections. Treatment was mainly based on high dose intravenous immunoglobulin. CONCLUSION: Although hematological impairment was the most frequent sign, B19V can affect multiple targets and lead to atypical manifestations. Because of its heterogeneous clinical presentation, B19V infection is likely under-diagnosed. Diagnosis of unusual B19V organ involvement needs combination of arguments which can include targeted tissue PCR.


Asunto(s)
Eritema Infeccioso , Trasplante de Células Madre Hematopoyéticas , Infecciones por Parvoviridae , Parvovirus B19 Humano , Humanos , Eritema Infeccioso/complicaciones , Estudios Retrospectivos , Parvovirus B19 Humano/genética , ADN Viral/análisis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre
6.
Virol J ; 19(1): 172, 2022 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-36316777

RESUMEN

Inborn errors of immunity (IEI) are a heterogeneous entity with an increasing number of late diagnoses. Besides infections, inflammatory manifestations are a growing part of the clinical landscape of IEI. These complications are of unknown causes and often lead to the prescription of immunosuppressive agents that worsen the underlying immune defect. We here report the case of an adult patient diagnosed with chronic Human Adenovirus C-1 arthritis in the setting of primary agammaglobulinemia. Metagenomic next-generation sequencing led to the correct diagnosis and high-dose intravenous immunoglobulins resulted in complete recovery. This observation gives new insights into adenoviral immunity and underlines the importance of metagenomics in the diagnosis of inflammatory manifestations in immunocompromised patients.


Asunto(s)
Adenovirus Humanos , Agammaglobulinemia , Artritis , Adulto , Humanos , Agammaglobulinemia/complicaciones , Agammaglobulinemia/diagnóstico , Adenoviridae/genética , Artritis/diagnóstico , Artritis/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico
7.
Exp Lung Res ; 48(1): 23-34, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34963427

RESUMEN

PURPOSE: Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. Materials and methods: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. "S-V4" for "Stringent V4" primer pair is used in two ongoing international projects "the Integrative Human microbiome project (iHMP)" and "the Earth microbiome project (EMP)." "R-V4" for "Relaxed V4" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. Results: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. "S-V4" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for "R-V4." The main difference related to poor Enterobacteriaceae detection with "R-V4" primers. Conclusions: Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R "S-V4" primer pair associated to Illumina® MiSeq paired-end sequencing.


Asunto(s)
Microbiota , Respiración Artificial , Bacterias/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Pulmón , Microbiota/genética , ARN Ribosómico 16S/genética , Respiración Artificial/efectos adversos
8.
J Clin Microbiol ; 59(5)2021 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-33568462

RESUMEN

Human adenovirus (HAdV) represents a major cause of mortality and morbidity in pediatric recipients of allogeneic hematopoietic stem cell transplants (HSCT). HAdV species F type 41 (HAdV-F41) infections in HSCT patients are scarce, whereas HAdV-F41 circulates commonly in healthy individuals. Between March and July 2018, HAdV-F41 infections were identified in four children (A, B, C, and E) who received allogeneic HSCT and one child before HSCT (D) at Robert Debré Hospital, Paris, France. We report here the clinical course of HAdV-F41 infection and the phylogenetic investigation to identify interpatient transmission. HAdV DNA was quantified in stool and plasma samples by real-time PCR. HAdV type was determined by sequencing of the fiber and hexon genes. Phylogenetic investigation was done with whole-genome sequences obtained by next-generation sequencing. HAdV loads in stool samples ranged from 6.60 to 10.10 log10 copies/ml. HAdV-F41 detection in plasma was observed in four patients, but no disseminated disease was reported. Two patients died, but neither death was attributed to HAdV. While sequencing limited to the fiber gene suggested a cluster with four patients, phylogenetic analysis with whole-genome sequencing (WGS) and HVR7 revealed a cluster that included three patients (C, D, and E), suggesting an interpatient transmission in that cluster and two other independent infections. HAdV-F41 levels in stool specimens of pediatric HSCT patients are high and represent a risk of interpatient transmission. WGS helped to identify related cases. Prompt detection of HAdV in stool and control measures are warranted to limit any risk of nosocomial transmission.


Asunto(s)
Infecciones por Adenovirus Humanos , Adenovirus Humanos , Trasplante de Células Madre Hematopoyéticas , Adenoviridae/genética , Infecciones por Adenovirus Humanos/epidemiología , Adenovirus Humanos/genética , Niño , Brotes de Enfermedades , Francia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Paris , Filogenia
9.
J Med Virol ; 93(11): 6371-6376, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34324206

RESUMEN

Human parainfluenza virus type 3 (HPIV-3) may cause lower respiratory tract infection disease (LRTI-D) after hematopoietic stem cell transplantation (HSCT). Most previous have studies focused on recipients of HSCT whereas data on characteristics and outcomes in patients with hematological malignancies (HMs) compared to non-hematological patients are limited. The prognostic value of viral load in respiratory specimens remains elusive. In a 2-year retrospective study, we determined the frequencies of LRTI-D in HM, HSCT, and in non-hematological patients, and HPIV-3 levels in respiratory tract secretions. Among 98 patients with HPIV-3 infection, including 31 HSCT and 40 HM, 36 had a diagnosis of LRTI-D. LRTI-D was significantly more frequent in patients with HM or HSCT (n = 32, 45.1%) than in non-hematological patients (n = 4, 14.8%) (p = 0.006). The median HPIV-3 loads were high in upper respiratory tract secretions regardless of the presence or absence of LRTI-D (8.3 log10 vs. 7.6 log10 TCID50 /106 cells). HPIV-3 loads in respiratory tract samples in HM were not significantly higher than those found in HSCT but significantly higher than in non-hematological patients (p = 0.007). In conclusion, LRTI-D was frequent in HM patients who were diagnosed with HPIV-3 infection.


Asunto(s)
Neoplasias Hematológicas/complicaciones , Virus de la Parainfluenza 3 Humana/patogenicidad , Infecciones por Paramyxoviridae/virología , Infecciones del Sistema Respiratorio/virología , Adolescente , Adulto , Anciano , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Adulto Joven
10.
Eur J Clin Microbiol Infect Dis ; 40(11): 2379-2388, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34342768

RESUMEN

Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the standard diagnostic test of coronavirus disease 2019. Our objectives were to assess, in real-life conditions, the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambulatory care. This was a prospective cohort study from 19 October through 18 December 2020 in two community COVID-19 screening centers in Paris, France. Two nasopharyngeal swabs and one saliva sample were simultaneously collected. Diagnostic accuracies of nasopharyngeal Ag testing and of three saliva NAAT methods were assessed as compared to nasopharyngeal NAAT. A total of 1452 ambulatory children and adults were included. Overall, 129/1443 (9%) participants tested positive on nasopharyngeal NAAT (102/564 [18%] in symptomatic and 27/879 [3%] in asymptomatic participants). Sensitivity was 94%, 23%, 96%, and 94% for the three different protocols of saliva NAAT and for the nasopharyngeal Ag test, respectively. Estimates of specificity were above 95% for all methods. Diagnostic accuracy was similar in symptomatic and asymptomatic individuals. Diagnostic accuracy of nasopharyngeal Ag testing and of saliva NAAT is similar to that of nasopharyngeal NAAT, subject to compliance with specific protocols for saliva. Registration number: NCT04578509.


Asunto(s)
Prueba de COVID-19/métodos , COVID-19/diagnóstico por imagen , Nasofaringe/virología , SARS-CoV-2/aislamiento & purificación , Saliva/virología , Manejo de Especímenes/métodos , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Técnicas de Amplificación de Ácido Nucleico/métodos , Paris , Pruebas en el Punto de Atención , Estudios Prospectivos , Sensibilidad y Especificidad
11.
Eur J Clin Microbiol Infect Dis ; 40(10): 2235-2241, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33782783

RESUMEN

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.


Asunto(s)
Anticuerpos Antivirales/sangre , Prueba Serológica para COVID-19/métodos , COVID-19/sangre , Inmunoensayo/métodos , SARS-CoV-2/inmunología , COVID-19/virología , Humanos , Inmunoensayo/economía , Inmunoglobulina M/sangre , Juego de Reactivos para Diagnóstico , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Sensibilidad y Especificidad
12.
Virologie (Montrouge) ; 25(1): 43-56, 2021 Feb 01.
Artículo en Francés | MEDLINE | ID: mdl-33650496

RESUMEN

Human adenoviruses (HAdV) infections are generally mild and resolve spontaneously in immunocompetent individuals. However, HAdV infections can have a major clinical impact in immunocompromised patients. HAdV infections are associated with high morbidity and mortality in recipients of allogeneic stem cell transplants, particularly children. There are currently no drug approved for the treatment of HAdV infections. Nevertheless, some nucleotide analogues are used under temporary authorization for use, such as cidofovir or brincidofovir. Cidofovir inhibits the replication of HAdV but its nephrotoxicity and its low tissue concentrations severely limit its use. Brincidofovir, a cidofovir prodrug, with a better bioavailability and no nephrotoxicity was evaluated in the treatment of HAdV infections, but its development was recently stopped and it is currently no longer available in ATU. Other molecules with anti-HAdV activity are still in early stages of development. Adoptive immunotherapy by adenovirus-specific T-cell transfer is an interesting option but should be anticipated in patients with high risks of disseminated infections. Given the small therapeutic panel available, it is critical to continue the search for new anti-HAdV molecules, which remains mainly conducted by academic laboratories.


Asunto(s)
Infecciones por Adenoviridae , Infecciones por Adenovirus Humanos , Adenovirus Humanos , Preparaciones Farmacéuticas , Infecciones por Adenoviridae/tratamiento farmacológico , Infecciones por Adenovirus Humanos/tratamiento farmacológico , Niño , Cidofovir , Humanos
13.
Virol J ; 17(1): 20, 2020 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-32014036

RESUMEN

BACKGROUND: Standardized and sensitive assays for Epstein Barr Virus (EBV) are needed to define universal cutoff for treatment initiation in allogeneic hematopoietic stem cells transplant recipients. In a context of accreditation and the availability of EBV international standard, we evaluated the Abbott RealTime EBV (RT) assay for EBV quantification in whole blood. METHODS: The RT assay was compared on 282 prospective clinical samples with the Artus EBV PCR Kit V1 assay (V1) and we analyzed the kinetics of EBV load in 11 patients receiving rituximab treatment. RESULTS: The estimated limit of detection was 88 IU/mL. The assay was linear (r2 = 0.9974) in the range of all samples tested (100 to 1,000,000 IU/mL). Intra-assay coefficients of variation (CV) ranged between 0.35 and 1.35%, and inter-assay CV between 3.40 and 4.5%. On samples above the limit of quantification, the two assays were strongly correlated. EBV RT values were on average 0.30 log10 IU/mL lower than those measured with the V1 assay. In patients treated with rituximab, the RT assay remained positive in 5 patients at the time it dropped below undetectable levels with the V1 assay. CONCLUSIONS: In conclusion, the RT assay is a reliable assay for EBV load in whole blood. Its sensitivity will enable to estimate the kinetics of EBV load and the impact of treatments to control EBV reactivations.


Asunto(s)
Sangre/virología , Infecciones por Virus de Epstein-Barr/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/aislamiento & purificación , Trastornos Linfoproliferativos/virología , Carga Viral/métodos , Automatización de Laboratorios , ADN Viral/sangre , Infecciones por Virus de Epstein-Barr/sangre , Humanos , Límite de Detección , Trastornos Linfoproliferativos/prevención & control , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Sensibilidad y Especificidad
14.
Am J Respir Crit Care Med ; 199(4): 518-528, 2019 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-30230909

RESUMEN

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.


Asunto(s)
Enfermedades Hematológicas/virología , Huésped Inmunocomprometido , Infecciones del Sistema Respiratorio/virología , Anciano , Enfermedad Crítica , Femenino , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/mortalidad , Mortalidad Hospitalaria , Humanos , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/mortalidad , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Infecciones por Paramyxoviridae/complicaciones , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/mortalidad , Infecciones por Picornaviridae/complicaciones , Infecciones por Picornaviridae/diagnóstico , Infecciones por Picornaviridae/mortalidad , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/mortalidad
15.
J Med Virol ; 89(11): 2003-2010, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28661055

RESUMEN

Prior to transplantation of hematopoietic stem cells or solid organ, donor and recipient EBV serostatus has to be determined to assess risks of post-transplant lymphoproliferative disorders. Sensitivity of EBV Viral capsid antigens (VCA) IgG and EBV nuclear antigen-1 (EBNA-1) is critical to define past infection and a good specificity of VCA IgM is required to avoid any disqualification of cord blood (CB) units. Architect™ EBV antibody panel (Architect assay) providing a high throughput was compared to a semi-automated ELISA (Etimax assays Diasorin) to assess sensitivities and specificities of VCA and EBNA-1 IgG and VCA IgM on 419 sera collected from immunocompromised patients (n = 184) and from pregnant women who agreed to give CB cells (n = 235). Intra and inter-assay coefficient of variations ranged from 1.63% to 4.8% for VCA IgM, VCA IgG, and EBNA-1 IgG. Index of VCA IgG and IgM and EBNA IgG of the two assays were highly correlated. The concordance in the interpretation between the two assays was moderate for VCA IgM (kappa = 0.5), substantial for VCA IgG (kappa = 0.60) and good for EBNA-1 IgG (kappa = 0.75). Using serial dilutions of positive controls and in accordance with clinical results VCA IgG and EBNA IgG were detected at lower dilutions with Architect than Etimax. Conversely, 96.1% (74/77) of samples negative with Architect and positive with Etimax for VCA IgM did not have any heterophile antibodies and had VCA IgG and EBNA IgG antibodies supporting past infections. Architect™ EBV serology panel provided good sensitivities and specificities for EBV serostatus determination prior to transplantation.


Asunto(s)
Anticuerpos Antivirales/sangre , Trasplante de Células Madre de Sangre del Cordón Umbilical , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/inmunología , Inmunoensayo/métodos , Mediciones Luminiscentes/métodos , Donantes de Tejidos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Virales/inmunología , Proteínas de la Cápside/inmunología , Niño , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Femenino , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Inmunidad Humoral , Huésped Inmunocomprometido , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Embarazo , Factores de Riesgo , Sensibilidad y Especificidad , Adulto Joven
17.
J Clin Microbiol ; 54(4): 928-33, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26763967

RESUMEN

Sensitive molecular assays have greatly improved the diagnosis of viral gastroenteritis. However, the proper preparation of stool samples for clinical testing remains an issue. bioMérieux has developed a stool preprocessing device (SPD) that includes a spoon for calibrated sampling and a vial containing buffer, glass beads, and two filters. The resulting stool filtrate is used for nucleic acid extraction. The purpose of this study was to evaluate the performance of the SPD for the quantification of human adenovirus (HAdV) DNA in stool samples collected from hematopoietic stem cell transplant (HSCT) recipients. HAdV DNA was quantified with the Adenovirus R-gene kit. The suitability of the device to reproducibly quantify HAdV DNA in stools using different extraction platforms (easyMAG and QIAsymphony) was determined using archived HAdV-positive stool samples. Coefficients of variation of HAdV DNA quantifications ranged from 1.79% to 1.83%, and no difference in quantification was observed between the two extraction systems. The HAdV DNA limit of quantification using the SPD was 3.75 log10copies/g of stool. HAdV DNA quantification using the SPD was then compared to that of the routine preprocessing technique on 75 fresh stool samples collected prospectively from pediatric HSCT recipients at risk for HAdV infections. Thirty-eight samples were HAdV DNA positive with both the SPD and routine preprocessing methods. HAdV DNA loads were on average 1.14-log10copies/g of stool higher with the SPD (P< 0.0001) than with routine methods. This new device enabled a standardized preparation of stool samples in <5 min and a reproducible and sensitive quantification of HAdV DNA. The use of the SPD for the detection of other gastrointestinal infections warrants further evaluation.


Asunto(s)
Infecciones por Adenoviridae/diagnóstico , Heces/virología , Gastroenteritis/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Manejo de Especímenes/métodos , Infecciones por Adenoviridae/virología , Preescolar , Gastroenteritis/virología , Humanos , Lactante , Recién Nacido , Técnicas de Diagnóstico Molecular/normas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Manejo de Especímenes/normas , Carga Viral/métodos
18.
Euro Surveill ; 21(19)2016 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-27195770

RESUMEN

In 2014, the United States (US) experienced a nationwide outbreak of enterovirus D68 (EV-D68) infection with 1,152 cases reported mainly in hospitalised children with severe asthma or bronchiolitis. Following the US alert, 11 laboratories of the French enterovirus (EV) surveillance network participated in an EV-D68 survey. A total of 6,229 respiratory samples, collected from 1 July to 31 December 2014, were screened for EV-D68 resulting in 212 EV-D68-positive samples. These 212 samples corresponded to 200 EV-D68 cases. The overall EV-D68 positivity rates among respiratory samples were of 5% (184/3,645) and 1.1% (28/2,584) in hospitalised children and adults respectively. The maximum weekly EV-D68 positivity rates were of 16.1% for children (n = 24/149; week 43) and 2.6% for adults (n = 3/115; week 42). Of 173 children with EV-D68 infection alone, the main symptoms were asthma (n = 83; 48.0%) and bronchiolitis (n = 37; 21.4%). One child developed acute flaccid paralysis (AFP) following EV-D68-associated pneumonia. Although there was no significant increase in severe respiratory tract infections reported to the French public health authorities, 10.7% (19/177) of the EV-D68 infected children and 14.3% (3/21) of the EV-D68 infected adults were hospitalised in intensive care units. Phylogenetic analysis of the viral protein 1 (VP1) sequences of 179 EV-D68 cases, revealed that 117 sequences (65.4%), including that of the case of AFP, belonged to the B2 variant of clade B viruses. Continuous surveillance of EV-D68 infections is warranted and could benefit from existing influenza-like illness and EV surveillance networks.


Asunto(s)
Enterovirus Humano D/aislamiento & purificación , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/epidemiología , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Vigilancia de la Población/métodos , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Infecciones por Enterovirus/virología , Femenino , Francia/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neumonía Viral/virología , Prevalencia , Factores de Riesgo , Distribución por Sexo , Adulto Joven
19.
Med Mycol ; 53(3): 241-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25550391

RESUMEN

Detection of viral and bacterial DNA in nasopharyngeal aspirates (NPAs) is now a routine practice in emergency cases of febrile pneumonia. We investigated whether Pneumocystis jirovecii DNA could also be detected in these cases by conducting retrospective screening of 324 consecutive NPAs from 324 adult patients (198 or 61% were immunocompromised) admitted with suspected pulmonary infections during the 2012 influenza epidemic season, using a real-time quantitative polymerase chain reaction (PCR) assay (PjqPCR), which targets the P. jirovecii mitochondrial large subunit ribosomal RNA gene. These NPAs had already been tested for 22 respiratory pathogens (18 viruses and 4 bacteria), but we found that 16 NPAs (4.9%) were PjqPCR-positive, making P. jirovecii the fourth most prevalent of the 23 microorganisms in the screen. Eleven of the 16 PjqPCR-positive patients were immunocompromised, and five had underlying pulmonary conditions. Nine NPAs were also positive for another respiratory pathogen. Six had PjqPCR-positive induced sputa less than 3 days after the NPA procedure, and five were diagnosed with pneumocystis pneumonia (four with chronic lymphoproliferative disorders and one AIDS patient). In all six available pairs quantification of P. jirovecii DNA showed fewer copies in NPA than in induced sputum and three PjqPCR-negative NPAs corresponded to PjqPCR-positive bronchoalveolar lavage fluids, underscoring the fact that a negative PjqPCR screen does not exclude a diagnosis of pneumocystosis. Including P. jirovecii DNA detection to the panel of microorganisms included in screening tests used for febrile pneumonia may encourage additional investigations or support use of anti-pneumocystis pneumonia prophylaxis in immunocompromised patients.


Asunto(s)
ADN de Hongos/aislamiento & purificación , Fiebre de Origen Desconocido/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Nasofaringe/microbiología , Pneumocystis carinii/aislamiento & purificación , Neumonía/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Femenino , Fiebre de Origen Desconocido/microbiología , Humanos , Masculino , Persona de Mediana Edad , Pneumocystis carinii/genética , Neumonía/microbiología , ARN Ribosómico/genética , Adulto Joven
20.
Biol Blood Marrow Transplant ; 20(8): 1238-41, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24732781

RESUMEN

Viral respiratory infections (VRIs) are frequent after hematopoietic stem cell transplantation and constitute a potential cause of mortality. We analyzed the incidence, risk factors, and prognosis of VRIs in a cohort of transplanted patients. More frequent viruses were human coronavirus and human rhinovirus followed by flu-like viruses and adenovirus. Risk factors for death were lymphocytopenia and high steroid dosage.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Infecciones del Sistema Respiratorio/diagnóstico , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo/efectos adversos , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/etiología , Infecciones del Sistema Respiratorio/virología , Acondicionamiento Pretrasplante/mortalidad , Trasplante Homólogo/mortalidad , Resultado del Tratamiento , Adulto Joven
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