RESUMEN
Worldwide outbreaks of enterovirus D68 (EV-D68) in 2014 and 2016 have caused serious respiratory and neurological disease. We collected samples from several European countries during the 2018 outbreak and determined 53 near full-length genome ('whole genome') sequences. These sequences were combined with 718 whole genome and 1,987 VP1-gene publicly available sequences. In 2018, circulating strains clustered into multiple subgroups in the B3 and A2 subclades, with different phylogenetic origins. Clusters in subclade B3 emerged from strains circulating primarily in the US and Europe in 2016, though some had deeper roots linking to Asian strains, while clusters in A2 traced back to strains detected in East Asia in 2015-2016. In 2018, all sequences from the USA formed a distinct subgroup, containing only three non-US samples. Alongside the varied origins of seasonal strains, we found that diversification of these variants begins up to 18 months prior to the first diagnostic detection during a EV-D68 season. EV-D68 displays strong signs of continuous antigenic evolution and all 2018 A2 strains had novel patterns in the putative neutralizing epitopes in the BC- and DE-loops. The pattern in the BC-loop of the USA B3 subgroup had not been detected on that continent before. Patients with EV-D68 in subclade A2 were significantly older than patients with a B3 subclade virus. In contrast to other subclades, the age distribution of A2 is distinctly bimodal and was found primarily among children and in the elderly. We hypothesize that EV-D68's rapid evolution of surface proteins, extensive diversity, and high rate of geographic mixing could be explained by substantial reinfection of adults. Better understanding of evolution and immunity across diverse viral pathogens, including EV-D68 and SARS-CoV-2, is critical to pandemic preparedness in the future.
Asunto(s)
COVID-19 , Enterovirus Humano D , Infecciones por Enterovirus , Infecciones del Sistema Respiratorio , Adulto , Anciano , Niño , Demografía , Brotes de Enfermedades , Enterovirus Humano D/genética , Infecciones por Enterovirus/epidemiología , Humanos , Filogenia , SARS-CoV-2RESUMEN
INTRODUCTION: It is unclear whether polyomavirus BK (BKPyV) microribonucleic acid (miRNA) measurement has additional diagnostic and predictive value in kidney transplant recipients (KTR) as compared to current methods of monitoring BKPyV DNA loads. PATIENTS AND METHODS: A retrospective, longitudinal study was performed in 30 KTR with BKPyV viruria (n = 10), BKPyV viremia (n = 10), or BKPyV-associated neuropathy (BKPyVAN) (n = 10). Bkv-miR-B1-3p and 5p and BKPyV DNA load were measured in urine and plasma and compared using receiver operating characteristic (ROC) curves. RESULTS: Levels of Bkv-miR-B1-3p and 5p and BKPyV DNA correlated strongly. Overall, mostly analog courses of urinary and plasma miRNA and DNA loads were observed. Areas under the ROC curves were not significantly different between miRNAs and DNA. Only, in contrast to BKPyV DNA load, BKPyV miRNA levels increased from 6 to 12 months in the viremia group, while in the BKPyVAN group, a decline was seen in both DNA and miRNA. CONCLUSIONS: In this study, we could not demonstrate an additional value of BKPyV miRNA detection compared to BKPyV DNA monitoring in the early phase after kidney transplantation. We did observe significant differences between the viremia and the BKPyVAN groups during follow-up. This study was performed with a small number of patients and therefore results should be verified in a larger patient cohort. Furthermore, future studies with larger patient groups are necessary to elucidate final clinical value of these data.
Asunto(s)
Virus BK , Enfermedades Renales , Trasplante de Riñón , MicroARNs , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Trasplante de Riñón/efectos adversos , ADN Viral , Estudios Retrospectivos , Viremia , Estudios Longitudinales , Virus BK/genética , Receptores de TrasplantesRESUMEN
BackgroundAcute flaccid myelitis (AFM) is a polio-like condition affecting mainly children and involving the central nervous system (CNS). AFM has been associated with different non-polio-enteroviruses (EVs), in particular EV-D68 and EV-A71. Reliable incidence rates in European countries are not available.AimTo report AFM incidence in children in the Netherlands and its occurrence relative to EV-D68 and EV-A71 detections.MethodsIn 10 Dutch hospitals, we reviewed electronic health records of patients diagnosed with a clinical syndrome including limb weakness and/or CNS infection and who were < 18 years old when symptoms started. After excluding those with a clear alternative diagnosis to AFM, those without weakness, and removing duplicate records, only patients diagnosed in January 2014-December 2019 were retained and further classified according to current diagnostic criteria. Incidence rates were based on definite and probable AFM cases. Cases' occurrences during the study period were co-examined with laboratory-surveillance detections of EV-D68 and EV-A71.ResultsAmong 143 patients included, eight were classified as definite and three as probable AFM. AFM mean incidence rate was 0.06/100,000 children/year (95% CI: -0.03 to 0.14). All patient samples were negative for EV-A71. Of respiratory samples in seven patients, five were EV-D68 positive. AFM cases clustered in periods with increased EV-D68 and EV-A71 detections.ConclusionsAFM is rare in children in the Netherlands. The temporal coincidence of EV-D68 circulation and AFM and the detection of this virus in several cases' samples support its association with AFM. Increased AFM awareness among clinicians, adequate diagnostics and case registration matter to monitor the incidence.
Asunto(s)
Enfermedades Virales del Sistema Nervioso Central , Enterovirus Humano A , Enterovirus Humano D , Infecciones por Enterovirus , Mielitis , Poliomielitis , Humanos , Niño , Adolescente , Países Bajos/epidemiología , Mielitis/diagnóstico , Mielitis/epidemiología , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/epidemiología , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/epidemiologíaRESUMEN
Current molecular detection methods for single or multiplex pathogens by real-time PCR generally offer great sensitivity and specificity. However, many infectious pathogens often result in very similar clinical presentations, complicating the test-order for physicians who have to narrow down the causative agent prior to in-house PCR testing. As a consequence, the intuitive response is to start empirical therapy to treat a broad spectrum of possible pathogens. Syndromic molecular testing has been increasingly integrated into routine clinical care, either to provide diagnostic, epidemiological or patient management information. These multiplex panels can be used to screen for predefined infectious disease pathogens simultaneously within a 1 h timeframe, creating opportunities for rapid diagnostics. Conversely, syndromic panels have their own challenges and must be adaptable to the evolving demands of the clinical setting. Firstly, questions have been raised regarding the clinical relevance of some of the targets included in the panels and secondly, there is the added expense of integration into the clinical laboratory. Here, we aim to discuss some of the factors that should be considered before performing syndromic testing rather than traditional low-plex in-house PCR.
Asunto(s)
Enfermedades Transmisibles , Técnicas de Diagnóstico Molecular , Enfermedades Transmisibles/diagnóstico , Humanos , Reacción en Cadena de la Polimerasa Multiplex , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y EspecificidadRESUMEN
Background: FLU-v is a broad-spectrum influenza vaccine that induces antibodies and cell-mediated immunity. Objective: To compare the safety, immunogenicity, and exploratory efficacy of different formulations and dosing regimens of FLU-v versus placebo. Design: Randomized, double-blind, placebo-controlled, single-center phase 2b clinical trial. (ClinicalTrials.gov: NCT02962908; EudraCT: 2015-001932-38). Setting: The Netherlands. Participants: 175 healthy adults aged 18 to 60 years. Intervention: 0.5-mL subcutaneous injection of 500 µg of adjuvanted (1 dose) or nonadjuvanted (2 doses) FLU-v (A-FLU-v or NA-FLU-v) or adjuvanted or nonadjuvanted placebo (A-placebo or NA-placebo) (2:2:1:1 ratio). Measurements: Vaccine-specific cellular responses at days 0, 42, and 180 were assessed via flow cytometry and enzyme-linked immunosorbent assay. Solicited information on adverse events (AEs) was collected for 21 days after vaccination. Unsolicited information on AEs was collected throughout the study. Results: The AEs with the highest incidence were mild to moderate injection site reactions. The difference between A-FLU-v and A-placebo in the median fold increase in secreted interferon-γ (IFN-γ) was 38.2-fold (95% CI, 4.7- to 69.7-fold; P = 0.001) at day 42 and 25.0-fold (CI, 5.7- to 50.9-fold; P < 0.001) at day 180. The differences between A-FLU-v and A-placebo in median fold increase at day 42 were 4.5-fold (CI, 2.3- to 9.8-fold; P < 0.001) for IFN-γ-producing CD4+ T cells, 4.9-fold (CI, 1.3- to 40.0-fold; P < 0.001) for tumor necrosis factor-α (TNF-α), 7.0-fold (CI, 3.5- to 18.0-fold; P < 0.001) for interleukin-2 (IL-2), and 1.7-fold (CI, 0.1- to 4.0-fold; P = 0.004) for CD107a. At day 180, differences were 2.1-fold (CI, 0.0- to 6.0-fold; P = 0.030) for IFN-γ and 5.7-fold (CI, 2.0- to 15.0-fold; P < 0.001) for IL-2, with no difference for TNF-α or CD107a. No differences were seen between NA-FLU-v and NA-placebo. Limitation: The study was not powered to evaluate vaccine efficacy against influenza infection. Conclusion: Adjuvanted FLU-v is immunogenic and merits phase 3 development to explore efficacy. Primary Funding Source: SEEK and the European Commission Directorate-General for Research and Innovation, European Member States within the UNISEC (Universal Influenza Vaccines Secured) project.
Asunto(s)
Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/inmunología , Adulto , Anticuerpos Antivirales/sangre , Relación Dosis-Respuesta Inmunológica , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Inmunidad Celular , Masculino , Persona de Mediana Edad , Países Bajos , Seguridad del PacienteRESUMEN
Laboratory preparedness with quality-assured diagnostic assays is essential for controlling the current coronavirus disease (COVID-19) outbreak. We conducted an external quality assessment study with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples to support clinical laboratories with a proficiency testing option for molecular assays. To analyse SARS-CoV-2 testing performance, we used an online questionnaire developed for the European Union project RECOVER to assess molecular testing capacities in clinical diagnostic laboratories.
Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/normas , Infecciones por Coronavirus/diagnóstico , Coronavirus/aislamiento & purificación , Técnicas de Diagnóstico Molecular/métodos , Pandemias , Neumonía Viral/diagnóstico , Betacoronavirus , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Servicios de Laboratorio Clínico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Brotes de Enfermedades , Europa (Continente) , Humanos , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/virología , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , SARS-CoV-2 , Sensibilidad y Especificidad , Encuestas y CuestionariosRESUMEN
BACKGROUND: In January 2017, the Dutch cervical cancer screening programme transitioned from cytomorphological to primary high-risk HPV (hrHPV) DNA screening, including the introduction of self-sampling, for women aged between 30 and 60 years. The Netherlands was the first country to switch to hrHPV screening at the national level. We investigated the health impact of this transition by comparing performance indicators from the new hrHPV-based programme with the previous cytology-based programme. METHODS: We obtained data from the Dutch nationwide network and registry of histo- and cytopathology (PALGA) for 454,573 women eligible for screening in 2017 who participated in the hrHPV-based programme between 1 January 2017 and 30 June 2018 (maximum follow-up of almost 21 months) and for 483,146 women eligible for screening in 2015 who participated in the cytology-based programme between 1 January 2015 and 31 March 2016 (maximum follow-up of 40 months). We compared indicators of participation (participation rate), referral (screen positivity; referral rate) and detection (cervical intraepithelial neoplasia (CIN) detection; number of referrals per detected CIN lesion). RESULTS: Participation in the hrHPV-based programme was significantly lower than that in the cytology-based programme (61% vs 64%). Screen positivity and direct referral rates were significantly higher in the hrHPV-based programme (positivity rate: 5% vs 9%; referral rate: 1% vs 3%). CIN2+ detection increased from 11 to 14 per 1000 women screened. Overall, approximately 2.2 times more clinical irrelevant findings (i.e. ≤CIN1) were found in the hrHPV-based programme, compared with approximately 1·3 times more clinically relevant findings (i.e. CIN2+); this difference was mostly due to a national policy change recommending colposcopy, rather than observation, of hrHPV-positive, ASC-US/LSIL results in the hrHPV-based programme. CONCLUSIONS: This is the first time that comprehensive results of nationwide implementation of hrHPV-based screening have been reported using high-quality data with a long follow-up. We have shown that both benefits and potential harms are higher in one screening round of a well-implemented hrHPV-based screening programme than in an established cytology-based programme. Lower participation in the new hrHPV programme may be due to factors such as invitation policy changes and the phased roll-out of the new programme. Our findings add further to evidence from trials and modelling studies on the effectiveness of hrHPV-based screening.
Asunto(s)
Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Tamizaje Masivo , Persona de Mediana Edad , Países Bajos , Estudios RetrospectivosRESUMEN
OBJECTIVES: Antiviral resistance in cytomegalovirus (CMV) may result from mutations in the molecular targets of antiviral agents. The aim of this study was to investigate both the prevalence of resistance-associated mutations and the factors associated with antiviral resistance in solid organ transplant (SOT) patients with repeated high CMV loads during antiviral treatment. METHODS: SOT patients were selected retrospectively, based on CMV loads of >30000 IU/mL at least twice in a period during which treatment was given. Patient samples were tested for antiviral resistance by Sanger sequencing the UL97 and UL54 genes of CMV, which code for the viral kinase and polymerase. Factors predisposing to and resulting from the development of antiviral resistance mutations were analysed. RESULTS: Multiple samples from 113 SOT patients were tested, showing resistance-associated mutations in 25 patients (22%). A further 20 (18%) patients showed mutations that were not known to be associated with antiviral resistance. Several factors were associated with development of resistance-associated mutations in UL97 as well as UL54, including human leucocyte antigen (HLA) mismatch, which occurred more frequently in the group of patients with resistance mutations. High-level resistance mutations were most frequently seen in UL97. CONCLUSIONS: This study shows that by selecting patients solely on the basis of virological response to treatment, more patients with antiviral resistance mutations are identified. In this study we confirm findings by other groups that primary infections are associated with resistance development. Moreover, we show that HLA mismatch is associated with the development of antiviral resistance, which suggests a role for host immunity in the development of resistance.
Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/virología , Citomegalovirus/efectos de los fármacos , Farmacorresistencia Viral , Mutación , Trasplante de Órganos , Adulto , Anciano , Citomegalovirus/genética , Femenino , Frecuencia de los Genes , Técnicas de Genotipaje , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Países Bajos/epidemiología , Prevalencia , Estudios Retrospectivos , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Acute flaccid myelitis is characterized by the combination of acute flaccid paralysis and a spinal cord lesion largely restricted to the gray matter on magnetic resonance imaging. The term acute flaccid myelitis was introduced in 2014 after the upsurge of pediatric cases in the USA with enterovirus D68 infection. Since then, an increasing number of cases have been reported worldwide. Whereas the terminology is new, the clinical syndrome has been recognized in the past in association with several other neurotropic viruses such as poliovirus.Conclusion: This review presents the current knowledge on acute flaccid myelitis with respect to the clinical presentation and its differential diagnosis with Guillain-Barré syndrome and acute transverse myelitis. We also discuss the association with enterovirus D68 and the presumed pathophysiological mechanism of this infection causing anterior horn cell damage. Sharing clinical knowledge and insights from basic research is needed to make progress in diagnosis, treatment, and prevention of this new polio-like disease. What is Known: ⢠Acute flaccid myelitis (AFM) is a polio-like condition characterized by rapid progressive asymmetric weakness, together with specific findings on MRI ⢠AFM has been related to different viral agents, but recent outbreaks are predominantly associated with enterovirus D68. What is New: ⢠Improving knowledge on AFM must increase early recognition and adequate diagnostic procedures by clinicians. ⢠The increasing incidence of AFM urges cooperation between pediatricians, neurologists, and microbiologists for the development of treatment and preventive options.
Asunto(s)
Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enterovirus Humano D , Infecciones por Enterovirus/diagnóstico , Mielitis/diagnóstico , Enfermedades Neuromusculares/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/epidemiología , Enfermedades Virales del Sistema Nervioso Central/terapia , Enfermedades Virales del Sistema Nervioso Central/virología , Diagnóstico Diferencial , Infecciones por Enterovirus/complicaciones , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/terapia , Salud Global , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/virología , Humanos , Mielitis/epidemiología , Mielitis/terapia , Mielitis/virología , Mielitis Transversa/diagnóstico , Mielitis Transversa/virología , Enfermedades Neuromusculares/epidemiología , Enfermedades Neuromusculares/terapia , Enfermedades Neuromusculares/virología , PronósticoRESUMEN
In June and July 2016, we identified 8 adults and 17 children with respiratory enterovirus D68 infections. Thirteen children required intensive care unit admission because of respiratory insufficiency, and 1 had concomitant acute flaccid myelitis. Phylogenetic analysis showed that all of 20 sequences obtained belong to the recently described clade B3.
Asunto(s)
Brotes de Enfermedades , Enterovirus Humano D/clasificación , Infecciones por Enterovirus/epidemiología , Filogenia , Infecciones del Sistema Respiratorio/epidemiología , Proteínas Virales/genética , Adulto , Anciano , Niño , Preescolar , Enterovirus Humano D/genética , Enterovirus Humano D/aislamiento & purificación , Infecciones por Enterovirus/transmisión , Infecciones por Enterovirus/virología , Humanos , Incidencia , Lactante , Unidades de Cuidado Intensivo Pediátrico , Persona de Mediana Edad , Países Bajos/epidemiología , Infecciones del Sistema Respiratorio/transmisión , Infecciones del Sistema Respiratorio/virologíaRESUMEN
BACKGROUND: Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. CASE PRESENTATION: A previously healthy 4-year-old boy presented with sudden weakness and limited mobility in his left arm. Two days earlier, he had an upper respiratory illness with mild fever. At admission, his physical examination showed that the child was febrile (38.5 °C) and alert but had a stiff neck and weakness in his left arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination showed a mild increase in white blood cell count (80/mm3, 41% neutrophils) and a slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular biology tests for detecting viral infection in CSF were negative. The patient was then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24 h, the muscle weakness extended to all four limbs, which exhibited greatly reduced mobility. Due to his worsening clinical prognosis, the child was transferred to our Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative, except for a focal signal alteration in the dorsal portion of the medulla oblongata, also involving the pontine tegmentum, whereas spine MRI showed an extensive signal alteration of the cervical and dorsal spinal cord reported as myelitis. Signal alteration was mainly localized in the central grey matter, most likely in the anterior horns. Molecular biology tests performed on nasopharyngeal aspirate and on bronchoalveolar lavage fluid were negative for bacteria but positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and intravenous immunoglobulins were administered. After 4 weeks of treatment, the signs and symptoms of AFM were significantly reduced, although some weakness and tingling remained in the patient's four limbs. MRI acquired after 3 weeks showed that the previously reported alterations were no longer present. CONCLUSION: This case suggests that EV-D68 is a neurotropic agent that can cause AFM and strains are circulating in Europe. EV-D68 disease surveillance is required to better understand EV-D68 pathology and to compare various strains that cause AFM.
Asunto(s)
Enterovirus Humano D/aislamiento & purificación , Infecciones por Enterovirus/diagnóstico , Hipotonía Muscular/etiología , Mielitis/etiología , Parálisis/etiología , Preescolar , Infecciones por Enterovirus/patología , Infecciones por Enterovirus/virología , Humanos , Italia , Masculino , Hipotonía Muscular/virología , Mielitis/virología , Parálisis/virologíaRESUMEN
BACKGROUND: It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). METHODS: A prospective, multicenter, open-label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL). Primary outcomes were incidence of BK viruria, BK viremia, and BKPyV-associated nephropathy (BKVAN). RESULTS: From 6 months, incidence of BK viruria in the MPS group (43.6%) was significantly higher than in the other groups (CsA: 16.9%, EVL: 19.8%) (P=.003). BKVAN was diagnosed in 3 patients, all treated with MPS (7.8%, P=.001). Longitudinal data analysis showed a lower BKPyV load and a significantly faster clearance of BK viruria in the CsA group compared to the MPS group (P=.03). CONCLUSIONS: Treatment with MPS was associated with an increased incidence of BK viruria. Dual immunosuppressive therapy with CsA and Pred was associated with the lowest rate of BKPyV replication and the fastest clearance of the virus.
Asunto(s)
Terapia de Inmunosupresión/efectos adversos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/epidemiología , Infecciones Tumorales por Virus/epidemiología , Adulto , Virus BK/aislamiento & purificación , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Humanos , Terapia de Inmunosupresión/métodos , Incidencia , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/sangre , Infecciones por Polyomavirus/orina , Infecciones por Polyomavirus/virología , Estudios Prospectivos , Receptores de Trasplantes , Infecciones Tumorales por Virus/sangre , Infecciones Tumorales por Virus/orina , Infecciones Tumorales por Virus/virología , Carga Viral/efectos de los fármacos , Viremia/epidemiología , Viremia/orinaRESUMEN
Enteroviruses (EVs) are a group of human and animal viruses that are capable of causing a variety of clinical syndromes. Different genotypes classified into species can be distinguished on the basis of sequence divergence in the VP1 capsid-coding region. Apparently new genotypes are discovered regularly, often as incidental findings in studies investigating respiratory syndromes or as part of poliovirus surveillance. Recently, some EVs have become recognized as significant respiratory pathogens, and a number of new genotypes belonging to species C have been identified. The circulation of these newly identified species C EVs, such as EV-C104, EV-C105, EV-C109, and EV-C117, nevertheless appears to be limited. In this report, we show the results of routine genotyping of all enteroviruses detected in our tertiary care hospital between January 2008 and April 2015. We detected 365 EVs belonging to 40 genotypes. Interestingly, several newly identified species C EVs were detected during the study period. Sequencing of the 5' untranslated region (5' UTR) of these viruses shows divergence in this region, which is a target region in many detection assays.
Asunto(s)
Infecciones por Enterovirus/virología , Enterovirus/clasificación , Enterovirus/genética , Genotipo , Regiones no Traducidas 5'/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Enterovirus/aislamiento & purificación , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Países Bajos , Análisis de Secuencia de ADN , Centros de Atención Terciaria , Proteínas Estructurales Virales/genética , Adulto JovenRESUMEN
The Dutch virus-typing network VIRO-TypeNed reported an increase in ECHOvirus 6 (E-6) infections with neurological symptoms in the Netherlands between June and August 2016. Of the 31 cases detected from January through August 2016, 15 presented with neurological symptoms. Ten of 15 neurological cases were detected in the same province and the identified viruses were genetically related. This report is to alert medical and public health professionals of the circulation of E-6 associated with neurological symptoms.
Asunto(s)
Brotes de Enfermedades , Echovirus 6 Humano/aislamiento & purificación , Infecciones por Echovirus/epidemiología , Meningitis Aséptica/epidemiología , Meningitis Aséptica/virología , Vigilancia de la Población/métodos , Salud Pública , Adolescente , Adulto , Líquido Cefalorraquídeo/virología , Niño , Preescolar , Sistemas de Información en Laboratorio Clínico , Echovirus 6 Humano/genética , Infecciones por Echovirus/diagnóstico , Infecciones por Echovirus/virología , Humanos , Persona de Mediana Edad , Países Bajos/epidemiología , Filogenia , Adulto JovenRESUMEN
VIRO-TypeNed is a collaborative molecular surveillance platform facilitated through a web-based database. Genetic data in combination with epidemiological, clinical and patient data are shared between clinical and public health laboratories, as part of the surveillance underpinning poliovirus eradication. We analysed the combination of data submitted from 2010 to 2014 to understand circulation patterns of non-polio enteroviruses (NPEV) of public health relevance. Two epidemiological patterns were observed based on VIRO-TypeNed data and classical surveillance data dating back to 1996: (i) endemic cyclic, characterised by predictable upsurges/outbreaks every two to four years, and (ii) epidemic, where rare virus types caused upsurges/outbreaks. Genetic analysis suggests continuous temporal displacement of virus lineages due to the accumulation of (silent) genetic changes. Non-synonymous changes in the antigenic B/C loop suggest antigenic diversification, which may affect population susceptibility. Infections were frequently detected at an age under three months and at an older, parenting age (25-49 years) pointing to a distinct role of immunity in the circulation patterns. Upsurges were detected in the summer and winter which can promote increased transmissibility underlying new (cyclic) upsurges and requires close monitoring. The combination of data provide a better understanding of NPEV circulation required to control and curtail upsurges and outbreaks.
Asunto(s)
Sistemas de Información en Laboratorio Clínico , Bases de Datos de Ácidos Nucleicos , Infecciones por Enterovirus/epidemiología , Enterovirus/genética , Laboratorios , Vigilancia de la Población/métodos , Brotes de Enfermedades/prevención & control , Enfermedades Endémicas , Enterovirus/aislamiento & purificación , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/virología , Epidemias , Humanos , Datos de Secuencia Molecular , Países Bajos/epidemiología , Salud Pública , SerotipificaciónRESUMEN
Torque teno virus (TTV) is emerging as a potential marker for monitoring immune status. In transplant recipients who are immunosuppressed, higher TTV DNA loads are observed than in healthy individuals. TTV load measurement may aid in optimizing immunosuppressive medication dosing in solid organ transplant recipients. Additionally, there is a growing interest in the role of HDL particles in immune function; therefore, assessment of both HDL concentrations and TTV load may be of interest in transplant recipients. The objective of this study was to analyze TTV loads and HDL parameters in serum samples collected at least one year post-transplantation from 656 stable outpatient kidney transplant recipients (KTRs), enrolled in the TransplantLines Food and Nutrition Cohort (Groningen, the Netherlands). Plasma HDL particles and subfractions were measured using nuclear magnetic resonance spectroscopy. Serum TTV load was measured using a quantitative real-time polymerase chain reaction. Associations between HDL parameters and TTV load were examined using univariable and multivariable linear regression. The median age was 54.6 [IQR: 44.6 to 63.1] years, 43.3% were female, the mean eGFR was 52.5 (±20.6) mL/min/1.73 m2 and the median allograft vintage was 5.4 [IQR: 2.0 to 12.0] years. A total of 539 participants (82.2%) had a detectable TTV load with a mean TTV load of 3.04 (±1.53) log10 copies/mL, the mean total HDL particle concentration was 19.7 (±3.4) µmol/L, and the mean HDL size was 9.1 (±0.5) nm. The univariable linear regression revealed a negative association between total HDL particle concentration and TTV load (st.ß = -0.17, 95% CI st.ß: -0.26 to -0.09, p < 0.001). An effect modification of smoking behavior influencing the association between HDL particle concentration and TTV load was observed (Pinteraction = 0.024). After adjustment for age, sex, alcohol intake, hemoglobin, eGFR, donor age, allograft vintage and the use of calcineurin inhibitors, the negative association between HDL particle concentration and TTV load remained statistically significant in the non-smoking population (st.ß = -0.14, 95% CI st.ß: -0.23 to -0.04, p = 0.006). Furthermore, an association between small HDL particle concentration and TTV load was found (st.ß = -0.12, 95% CI st.ß: -0.22 to -0.02, p = 0.017). Higher HDL particle concentrations were associated with a lower TTV load in kidney transplant recipients, potentially indicative of a higher immune function. Interventional studies are needed to provide causal evidence on the effects of HDL on the immune system.
Asunto(s)
Trasplante de Riñón , Torque teno virus , Humanos , Femenino , Persona de Mediana Edad , Masculino , Receptores de Trasplantes , Trasplante de Riñón/efectos adversos , Pacientes Ambulatorios , Torque teno virus/genética , Lipoproteínas HDLRESUMEN
Results from microbiological and epidemiological investigations, as well as mathematical modelling, show that the transmission dynamics of nosocomial pathogens, especially of multiple antibiotic-resistant bacteria, is not exclusively amenable to single-hospital infection prevention measures. Crucially, their extent of spread depends on the structure of an underlying "healthcare network", as determined by inter-institutional referrals of patients. The current trend towards centralized healthcare systems favours the spread of hospital-associated pathogens, and must be addressed by coordinated regional or national approaches to infection prevention in order to maintain patient safety. Here we review recent advances that support this hypothesis, and propose a "next-generation" network-approach to hospital infection prevention and control.
Asunto(s)
Control de Enfermedades Transmisibles/métodos , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Atención a la Salud/organización & administración , Infección Hospitalaria/transmisión , Política de Salud , HumanosRESUMEN
Introduction: High cycle threshold values (Ct) value) results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be true infections or false-positive results. Misinterpretation of results has negative consequences. Goal of this study was to evaluate quantitative real-time polymerase chain reaction (qPCR) results with high Ct-values, to reach a point where a correct interpretation can be given. Methods: High Ct-value results of SARS-CoV-2 in respiratory samples taken between April 2020 and January 2021 were analysed. Three different SARS-CoV-2 qPCR assays (in-house, Alinity M and Xpert Xpress) were used for screening patients and healthcare workers (HCW). High Ct-value results were defined as "inconclusive". The Ct-value cut-off for the interpretation of the test as "positive" and "inconclusive" were based on quality assurance panel results and manufacturers' instructions. Results: Out of totally 50.295 samples tested for SARS-CoV-2, the in-house and Alinity M qPCR together yielded 379 inconclusive results. A second sample existed for 217 samples, allowing dynamics of the PCR in time. Of these, 187 were negative (86%), 11 again inconclusive (5%) and 19 positive (9%). Sixteen out of 19 persons with a positive result were HCW, 14 (74%) had a link to a SARS-CoV-2 infected person. The majority of inconclusive results detected with the Xpert Xpress (n=45 of 3603), were related to individuals with a known history of SARS-CoV-2 infection (n=28, 62%). Conclusion: This study shows the importance of re-testing inconclusive SARS-CoV-2 qPCR results. Only then, the correct (true or false) interpretation can be given, leading to the right measures.
RESUMEN
Torquetenovirus (TTV), a small, single stranded anellovirus, is currently being explored as a marker of immunocompetence in patients with immunological impairment and inflammatory disorders. TTV has an extremely high prevalence and is regarded as a part of the human virome, the replication of which is controlled by a functioning immune system. The viral load of TTV in plasma of individuals is thought to reflect the degree of immunosuppression. Measuring and quantifying this viral load is especially promising in organ transplantation, as many studies have shown a strong correlation between high TTV loads and increased risk of infection on one side, and low TTV loads and an increased risk of rejection on the other side. As clinical studies are underway, investigating if TTV viral load measurement is superior for gauging antirejection therapy compared to medication-levels, some aspects nevertheless have to be considered. In contrast with medication levels, TTV loads have to be interpreted bearing in mind that viruses have properties including transmission, tropism, genotypes and mutations. This narrative review describes the potential pitfalls of TTV measurement in the follow-up of solid organ transplant recipients and addresses the questions which remain to be answered.
RESUMEN
INTRODUCTION: Public health measures aimed at controlling transmission of SARS-CoV-2, otherwise known as "lockdown" measures, had profound effects on circulation of non-SARS viruses, many of which decreased to very low levels. The interrupted transmission of these viruses may have lasting effects. Some of the influenza clades seem to have disappeared during this period, a phenomenon which is described as a "funnel effect". It is currently unknown if the lockdown measures had any effect on the diversity of circulating viruses, other than influenza. Enteroviruses are especially interesting in this context, as the clinical presentation of an infection with a particular enterovirus-type may be clade-dependent. METHODS AND MATERIALS: Enteroviruses were detected in clinical materials using a 5'UTR-based detection PCR, and partial VP-1 sequences were obtained, using methods described before. All samples with EV detections from a large part of the Netherlands were included in the study. The samples originated from general practitioners, general hospitals, university hospitals and public health offices. RESULTS: Five EV-genotypes circulated in significant numbers before and after the lockdown, EV-D68, E-11, CV-A6, CV-B5 and CV-A2. All five genotypes showed decreased genetic diversity after the lockdown, and four indicate a significant number of sequences clustering together with a very high sequence homology. Moreover, children with E-11 and CV-B5 detections were significantly older after the lockdown than before. CONCLUSIONS: The reduced enterovirus transmission in the Netherlands during the pandemic, seems to have led to a decrease in genetic diversity in the five most commonly detected enterovirus serotypes.