RESUMEN
We detected a novel GII.4 variant with an amino acid insertion at the start of epitope A in viral protein 1 of noroviruses from the United States, Gabon, South Africa, and the United Kingdom collected during 2017-2022. Early identification of GII.4 variants is crucial for assessing pandemic potential and informing vaccine development.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Humanos , Gastroenteritis/epidemiología , Norovirus/genética , Infecciones por Caliciviridae/epidemiología , Genotipo , Pandemias , FilogeniaRESUMEN
As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.
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Infecciones por Adenovirus Humanos , Coinfección , Dependovirus , Hepatitis , Niño , Humanos , Enfermedad Aguda , Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/virología , Coinfección/epidemiología , Coinfección/virología , Dependovirus/genética , Dependovirus/aislamiento & purificación , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/virología , Hepatitis/epidemiología , Hepatitis/virología , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 6/aislamiento & purificación , Enterovirus Humano A/aislamiento & purificación , Virus Helper/aislamiento & purificaciónRESUMEN
We report 5 clustered acute gastroenteritis outbreaks in long-term care facilities in Utah, USA, that were linked to healthcare employees working at multiple facilities. Four outbreaks were caused by norovirus genotype GIX. We recommend continued norovirus surveillance and genotyping to determine contributions of this genotype to norovirus outbreaks.
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Infecciones por Caliciviridae , Norovirus , Humanos , Norovirus/genética , Infecciones por Caliciviridae/epidemiología , Cuidados a Largo Plazo , Utah/epidemiología , Brotes de Enfermedades , GenotipoRESUMEN
Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Adulto , Niño , Genotipo , Humanos , Hígado , FilogeniaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 85.1-86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis.
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COVID-19/diagnóstico , Nasofaringe/virología , ARN Viral/metabolismo , SARS-CoV-2/genética , Área Bajo la Curva , COVID-19/metabolismo , COVID-19/patología , COVID-19/virología , Biblioteca de Genes , Humanos , Aprendizaje Automático , ARN Viral/sangre , Curva ROC , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2/aislamiento & purificación , Sensibilidad y Especificidad , TranscriptomaRESUMEN
BACKGROUND: Noroviruses are the major cause of acute gastroenteritis (AGE) in people of all ages globally. Standardized genotyping is key for outbreak investigations and surveillance networks. OBJECTIVE: Here we describe the validation of a one-step conventional RT-PCR assay for sequence-based dual typing of GI and GII noroviruses. This polymerase (P) and capsid (C) dual typing assay uses a combination of previously published oligonucleotide primers amplifying a genomic region spanning the 3'-end of ORF1 and 5'end of ORF2 resulting in a 579 bp product for GI and 570 bp product for GII viruses. RESULTS: The limit of detection of the assay ranged from 5 to 50 copies of viral RNA per reaction for GI and GII. To validate the assay, we tested 2,663 noroviruspositive stool samples from outbreaks and sporadic cases of AGE in Bangladesh, Guatemala, Peru, and USA collected between 2010-2019, of which 2,392 (90 %) were genotyped successfully. Most of the known genotypes infecting humans (GI (n = 9) and GII (n = 23)) and P types (GI (n = 15), GII, (n = 20)) could be detected. The remaining 270 samples had low viral load (Ct > 30) by real-time RT-PCR. A panel of 166 samples positive for other enteric viruses (rotavirus, astrovirus, sapovirus, adenovirus type 40/41) tested negative. CONCLUSION: The use of broadly reactive genotyping assays greatly strengthens exchange of standardized genotype data globally to monitor trends in genotype diversity which is important for both the development of vaccines and to measure their impact.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Infecciones por Caliciviridae/epidemiología , Heces , Gastroenteritis/epidemiología , Genotipo , Humanos , Norovirus/genética , Filogenia , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, with >365,000 cases in California as of 17 July 2020. We investigated the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning nine counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least seven different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington state, with lack of a predominant lineage and limited transmission among communities. Lineages associated with outbreak clusters in two counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain the spread of SARS-CoV-2 in California and other states.
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Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Genoma Viral , Filogenia , Neumonía Viral/epidemiología , Neumonía Viral/virología , COVID-19 , California/epidemiología , Infecciones por Coronavirus/transmisión , Monitoreo Epidemiológico , Humanos , Pandemias , Neumonía Viral/transmisión , SARS-CoV-2 , Alineación de Secuencia , Navíos , Viaje , WashingtónRESUMEN
An outbreak of novel betacoronavirus, SARS-CoV-2 (formerly named 2019-nCoV), began in Wuhan, China in December 2019 and the COVID-19 disease associated with infection has since spread rapidly to multiple countries. Here we report the development of SARS-CoV-2 DETECTR, a rapid (~30 min), low-cost, and accurate CRISPR-Cas12 based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated this method using contrived reference samples and clinical samples from infected US patients and demonstrated comparable performance to the US CDC SARS-CoV-2 real-time RT-PCR assay.
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The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.
RESUMEN
The Camp Fire, California's deadliest wildfire, began November 8, 2018, and was extinguished November 25 (1). Approximately 1,100 evacuees from the fire sought emergency shelter. On November 10, acute gastroenteritis (AGE) was reported in two evacuation shelters; norovirus illness was suspected, because it is commonly detected in shelter-associated AGE outbreaks. Norovirus is highly contagious and resistant to several disinfectants. Butte County Public Health Department (BCPHD), assisted by the California Department of Public Health (CDPH), initiated active surveillance to identify cases, confirm the etiology, and assess shelter infection prevention and control (IPC) practices to guide recommendations. During November 8-30, a total of 292 patients with AGE were identified among nine evacuation shelters; norovirus was detected in 16 of 17 unique patient stool specimens. Shelter IPC assessments revealed gaps in illness surveillance, isolation practices, cleaning, disinfection, and handwashing. CDPH and BCPHD collaborated with partner agencies to implement AGE screening, institute isolation protocols and 24-hour cleaning services, and promote proper hand hygiene. During disasters with limited resources, damaged infrastructure, and involvement of multiple organizations, establishing shelter disease surveillance and IPC is difficult. However, prioritizing effective surveillance and IPC at shelter activation is necessary to prevent, identify, and contain outbreaks.
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Infecciones por Caliciviridae/epidemiología , Brotes de Enfermedades , Refugio de Emergencia , Incendios Forestales , Anciano , California/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to produce a global pandemic. We report development of a rapid (<40 min), easy-to-implement and accurate CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US Centers for Disease Control and Prevention SARS-CoV-2 real-time RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.
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Betacoronavirus/aislamiento & purificación , Sistemas CRISPR-Cas , Técnicas de Laboratorio Clínico , Técnicas de Amplificación de Ácido Nucleico/métodos , Betacoronavirus/genética , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/virología , ARN Guía de Kinetoplastida/genética , SARS-CoV-2 , Factores de TiempoRESUMEN
We report the nearly complete genome sequence of a human enterovirus, a strain of echovirus 30, obtained from a cerebrospinal fluid specimen from a teenaged patient with aseptic meningitis in September 2017.
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On June 22, 2017, the Los Angeles County Department of Public Health (LAC DPH) was notified of seven patients who were seen at an eye care clinic on June 8, 2017, and later developed symptoms of epidemic keratoconjunctivitis (EKC). EKC is a contagious, severe form of viral conjunctivitis that can cause pain and blurred vision for up to 4 weeks (1). LAC DPH conducted an investigation, which identified 17 patients with EKC, including 15 who had visited the optometry clinic and two who were household contacts of clinic patients. Observations in the clinic found deficiencies in disinfection of tonometers (an instrument connected to a slit lamp and used to test for glaucoma by measuring intraocular pressure) and multiuse eye drop administration. Staff member education and revision of disinfection practices interrupted further transmission. Patient specimens tested positive for human adenovirus (HAdV) type D53 (HAdV-53). As the first documented EKC outbreak associated with HAdV-D53 in the United States, this outbreak highlights the need for rigorous implementation of recommended infection prevention practices in eye care settings.
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Adenoviridae/aislamiento & purificación , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Queratoconjuntivitis/epidemiología , Optometría , Adulto , Anciano , Análisis por Conglomerados , Infección Hospitalaria/transmisión , Femenino , Humanos , Los Angeles/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
We report here two genome sequences of a newly designated rhinovirus genotype, RV-C56, which were obtained from respiratory specimens of three patients with acute respiratory illness in 2016 and 2017. To our knowledge, these sequences represent the first near-complete genomes for RV-C56 strains.
RESUMEN
BACKGROUND: Sapoviruses are responsible for sporadic and epidemic acute gastroenteritis worldwide. Sapovirus typing protocols have a success rate as low as 43% and relatively few complete sapovirus genome sequences are available to improve current typing protocols. OBJECTIVE/STUDY DESIGN: To increase the number of complete sapovirus genomes to better understand the molecular epidemiology of human sapovirus and to improve the success rate of current sapovirus typing methods, we used deep metagenomics shotgun sequencing to obtain the complete genomes of 68 sapovirus samples from four different countries across the Americas (Guatemala, Nicaragua, Peru and the US). RESULTS: VP1 genotyping showed that all sapovirus sequences could be grouped in the four established genogroups (GI (nâ¯=â¯13), GII (nâ¯=â¯30), GIV (nâ¯=â¯23), GV (nâ¯=â¯2)) that infect humans. They include the near-complete genome of a GI.6 virus and a recently reported novel GII.8 virus. Sequences of the complete RNA-dependent RNA polymerase gene could be grouped into three major genetic clusters or polymerase (P) types (GI.P, GII.P and GV.P) with all GIV viruses harboring a GII polymerase. One (GII.P-GII.4) of the new 68 sequences was a recombinant virus with the hotspot between the NS7 and VP1 regions. CONCLUSIONS: Analyses of this expanded database of near-complete sapovirus sequences showed several mismatches in the genotyping primers, suggesting opportunities to revisit and update current sapovirus typing methods.
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Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Variación Genética , Sapovirus/clasificación , Sapovirus/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Américas/epidemiología , Niño , Preescolar , Femenino , Gastroenteritis/epidemiología , Gastroenteritis/virología , Genoma Viral , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Masculino , Metagenómica , Persona de Mediana Edad , Epidemiología Molecular , Sapovirus/genética , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Before the introduction of rotavirus vaccine in 2006, rotavirus was the most common cause of severe diarrhea among U.S. children (1). Currently, two rotavirus vaccines are licensed for use in the United States, both of which have demonstrated good field effectiveness (78%-89%) against moderate to severe rotavirus illness (2), and the use of these vaccines has substantially reduced the prevalence of rotavirus in the United States (3). However, the most recent national vaccine coverage estimates indicate lower full rotavirus vaccine-series completion (73%) compared with receipt of at least 3 doses of vaccines containing diphtheria, tetanus, and pertussis antigens (95%), given on a similar schedule to rotavirus vaccines (4). In the postvaccine era in the United States, rotavirus activity persists in a biennial pattern (3). This report describes three rotavirus outbreaks that occurred in California in 2017. One death was reported; however, the majority of cases were associated with mild to moderate illness, and illness occurred across the age spectrum as well as among vaccinated children. Rotavirus vaccines are designed to mimic the protective effects of natural infection and are most effective against severe rotavirus illness (2). Even in populations with high vaccination coverage, some rotavirus infections and mild to moderate illnesses will occur. Rotavirus vaccination should continue to be emphasized as the best means of reducing disease prevalence in the United States.
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Instituciones de Vida Asistida , Guarderías Infantiles , Brotes de Enfermedades/estadística & datos numéricos , Instituciones de Salud , Infecciones por Rotavirus/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , California/epidemiología , Niño , Preescolar , Humanos , Lactante , Persona de Mediana Edad , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Adulto JovenRESUMEN
Here, we report the full coding sequence of rhinovirus C47 (RV-C47), obtained from a patient respiratory sample collected during an acute respiratory illness investigation in Butte County, California, in January 2017. This is the first whole-genome sequence of RV-C47 to be reported.
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During October 2010-July 2011, 1.0% of pandemic (H1N1) 2009 viruses in the United States were oseltamivir resistant, compared with 0.5% during the 2009-10 influenza season. Of resistant viruses from 2010-11 and 2009-10, 26% and 89%, respectively, were from persons exposed to oseltamivir before specimen collection. Findings suggest limited community transmission of oseltamivir-resistant virus.
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Antivirales/uso terapéutico , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/epidemiología , Oseltamivir/uso terapéutico , Pandemias , Adulto , Antivirales/farmacología , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/tratamiento farmacológico , Gripe Humana/mortalidad , Gripe Humana/virología , Masculino , Oseltamivir/farmacología , Prevalencia , Estados Unidos/epidemiologíaRESUMEN
During April 2009-June 2010, thirty-seven (0.5%) of 6,740 pandemic (H1N1) 2009 viruses submitted to a US surveillance system were oseltamivir resistant. Most patients with oseltamivir-resistant infections were severely immunocompromised (76%) and had received oseltamivir before specimen collection (89%). No evidence was found for community circulation of resistant viruses; only 4 (unlinked) patients had no oseltamivir exposure.
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Antivirales/farmacología , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana , Oseltamivir/farmacología , Pandemias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Niño , Preescolar , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Huésped Inmunocomprometido , Lactante , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/epidemiología , Gripe Humana/mortalidad , Gripe Humana/fisiopatología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Neuraminidasa/antagonistas & inhibidores , Oseltamivir/administración & dosificación , Vigilancia de la Población/métodos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Encephalitis is a complex, debilitating, and sometimes fatal neurologic condition to which children are especially prone. Mycoplasma pneumoniae, a common respiratory pathogen, has been implicated as an etiology of encephalitis. Evidence for recent or acute M. pneumoniae infection has been demonstrated in limited studies of both pediatric and adult patients with encephalitis. PATIENTS AND METHODS: Unexplained encephalitis cases are referred to the California Encephalitis Project for diagnostic testing. Serum, cerebrospinal fluid, and respiratory specimens are tested by polymerase chain reaction and serology methods for the presence of multiple pathogens, including M. pneumoniae. M. pneumonia-associated cases of encephalitis were compared with other bacterial agents, herpes simplex virus 1, and enterovirus. RESULTS: Of 1988 patients referred to the California Encephalitis Project, evidence of acute M. pneumoniae infection was found in 111 patients, of which 84 (76%) were pediatric patients. Eighty percent of the 84 patients were positive for M. pneumoniae by serology alone. Cerebrospinal fluid polymerase chain reaction for M. pneumoniae was rarely positive (2%). Patients with M. pneumoniae-associated pediatric encephalitis were a median of 11 years old, progressed rapidly (median: 2 days from onset to hospitalization), and were often in the ICU (55%). Symptoms included fever (70%), lethargy (68%), and altered consciousness (58%). Gastrointestinal (45%) and respiratory (44%) symptoms were less common. Compared with patients with other bacterial as well as viral agents, patients with M. pneumoniae-associated encephalitis had fewer seizures and less-severe hospital courses. CONCLUSIONS: M. pneumoniae is the most common agent implicated in the California Encephalitis Project. Patients with M. pneumoniae-associated encephalitis are predominantly pediatric, and their presentations are clinically similar to enterovirus encephalitis, although they frequently require intensive care with prolonged hospitalizations. Given that M. pneumoniae infection is found more than any other pathogen, increased emphasis should be placed on elucidating the role and mechanism of M. pneumoniae in encephalitis.