Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 46 Records) |
Query Trace: Barclay S[original query] |
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An updated framework for SARS-CoV-2 variants reflects the unpredictability of viral evolution
Subissi L , Otieno JR , Worp N , Attar Cohen H , Oude Munnink BB , Abu-Raddad LJ , Alm E , Barakat A , Barclay WS , Bhiman JN , Caly L , Chand M , Chen M , Cullinane A , de Oliveira T , Drosten C , Druce J , Effler P , El Masry I , Faye A , Ghedin E , Grant R , Haagmans BL , Happi C , Herring BL , Hodcroft EB , Ikejezie J , Katawera V , Kassamali ZA , Leo YS , Leung GM , Kondor RJ , Marklewitz M , Mendez-Rico J , Melhem NM , Munster V , Nahapetyan K , Naindoo D , Oh DY , Peacock TP , Peiris M , Peng Z , Poon LLM , Rambaut A , Saha S , Shen Y , Siqueira MM , Volz E , Tessema SK , Thiel V , Triki H , van der Werf S , von Eije K , Cunningham J , Koopmans MPG , von Gottberg A , Agrawal A , Van Kerkhove MD . Nat Med 2024 |
Emergence of novel norovirus GII.4 variant
Chhabra P , Tully DC , Mans J , Niendorf S , Barclay L , Cannon JL , Montmayeur AM , Pan CY , Page N , Williams R , Tutill H , Roy S , Celma C , Beard S , Mallory ML , Manouana GP , Velavan TP , Adegnika AA , Kremsner PG , Lindesmith LC , Hué S , Baric RS , Breuer J , Vinjé J . Emerg Infect Dis 2024 30 (1) 163-167 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. |
SARS-CoV-2 surface contamination in metro-Atlanta grocery stores
Brown TW , Park GW , Wittry B , Barclay L , Person M , Relja B , Daly S , Chhabra P , Kincaid E , Johnson J , Ahmad A , Herzegh O , Vinjé J , Murphy J . PLoS One 2023 18 (9) e0291747 While the COVID-19 pandemic has had a detrimental impact on many businesses worldwide, essential businesses, such as grocery stores, continued to operate despite potential disease transmission. Although the principal mode by which people are infected with SARS-CoV-2, the virus that causes COVID-19, is through exposure to respiratory droplets and very small particles carrying infectious virus, contaminated surfaces might play a role in transmission. We collected swab samples from frequently touched surfaces, including grocery carts, touchscreen monitors, credit card keypads, pharmacy counters, self-service food utensils, and refrigerator and freezer handles, in two metro-Atlanta grocery stores over the course of two sampling events in March 2021. Of the 260 swab samples collected, 6 (2.3%) samples were positive for SARS-CoV-2 RNA by reverse transcriptase quantitative polymerase chain reaction. Positive samples were collected from pharmacy (12.0% [3/25] samples), refrigerator/freezer aisles (2.5% [1/39] samples), and self-service food court (5.0% [2/40] samples) areas. Table/counter edge and underside surfaces represented 33% (2/6) of positive samples. These data suggest that risk of exposure to SARS-CoV-2 from frequently touched surfaces in grocery store settings is likely low; however, more frequent cleaning of surfaces in pharmacy and self-service food courts might be warranted. |
Robustness of the ferret model for influenza risk assessment studies: a cross-laboratory exercise (preprint)
Belser JA , Lau EHY , Barclay W , Barr IG , Chen H , Fouchier RAM , Hatta M , Herfst S , Kawaoka Y , Lakdawala SS , Lee LYY , Neumann G , Peiris M , Perez DR , Russell C , Subbarao K , Sutton TC , Webby RJ , Yang H , Yen HL . bioRxiv 2022 2022.04.02.486825 Ferrets represent the preferred animal model for assessing the transmission potential of newly emerged zoonotic influenza viruses. However, heterogeneity among established experimental protocols and facilities across different laboratories may lead to variable results, complicating interpretation of transmission experimental data. Between 2018-2020, a global exercise was conducted by 11 participating laboratories to assess the range of variation in ferret transmission experiments using two common stock H1N1 influenza viruses that possess different transmission characteristics in ferrets. Inoculation route, dose, and volume were standardized, and all participating laboratories followed the same experimental conditions for respiratory droplet transmission, including a strict 1:1 donor:contact ratio. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored throughout. Overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. To attain high confidence in identifying zoonotic influenza viruses with moderate-to-high or low transmissibility, our analyses support that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment.Competing Interest StatementThe authors have declared no competing interest. |
An early warning system for emerging SARS-CoV-2 variants.
Subissi L , von Gottberg A , Thukral L , Worp N , Oude Munnink BB , Rathore S , Abu-Raddad LJ , Aguilera X , Alm E , Archer BN , Attar Cohen H , Barakat A , Barclay WS , Bhiman JN , Caly L , Chand M , Chen M , Cullinane A , de Oliveira T , Drosten C , Druce J , Effler P , El Masry I , Faye A , Gaseitsiwe S , Ghedin E , Grant R , Haagmans BL , Herring BL , Iyer SS , Kassamali Z , Kakkar M , Kondor RJ , Leite JA , Leo YS , Leung GM , Marklewitz M , Moyo S , Mendez-Rico J , Melhem NM , Munster V , Nahapetyan K , Oh DY , Pavlin BI , Peacock TP , Peiris M , Peng Z , Poon LLM , Rambaut A , Sacks J , Shen Y , Siqueira MM , Tessema SK , Volz EM , Thiel V , van der Werf S , Briand S , Perkins MD , Van Kerkhove MD , Koopmans MPG , Agrawal A . Nat Med 2022 28 (6) 1110-1115 Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic. | | In June 2020, the World Health Organization (WHO) SARS-CoV-2 evolution working group was established to track SARS-CoV-2 variants and their specific genetic changes and to monitor viral characteristics and their impact on medical and non-medical countermeasures, including vaccines against COVID-19. In November 2021, this working group transitioned to a formal WHO Technical Advisory Group on Virus Evolution (TAG-VE), with the aim of developing and implementing a global risk-monitoring framework for SARS-CoV-2 variants, based on a multidisciplinary approach that includes in silico, virological, clinical and epidemiological data. |
Notes from the field: Norovirus outbreaks reported through norostat - 12 states, August 2012-July 2022
Kambhampati AK , Wikswo ME , Barclay L , Vinjé J , Mirza SA . MMWR Morb Mortal Wkly Rep 2022 71 (38) 1222-1224 Norovirus is the leading cause of acute gastroenteritis in the United States (1). In April 2020, the incidence of norovirus outbreaks in the United States declined substantially, likely because of implementation of COVID-19–related nonpharmaceutical interventions, such as facility closures, social distancing, and increased hand hygiene (2). Similar declines were observed in other countries (3,4). Norovirus outbreaks in the United States increased rapidly starting in January 2022, approaching prepandemic (i.e., 2012–2019) levels. Norovirus transmission can be prevented by thorough handwashing and proper cleaning and disinfection of contaminated surfaces © 2022, MMWR Recommendations and Reports.All Rights Reserved. |
Robustness of the ferret model for influenza risk assessment studies: A cross-laboratory exercise
Belser JA , Lau EHY , Barclay W , Barr IG , Chen H , Fouchier RAM , Hatta M , Herfst S , Kawaoka Y , Lakdawala SS , Lee LYY , Neumann G , Peiris M , Perez DR , Russell C , Subbarao K , Sutton TC , Webby RJ , Yang H , Yen HL . mBio 2022 13 (4) e0117422 Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information supporting public health efforts. Ferret transmission experiments have been utilized to predict the human-to-human transmission potential of novel influenza viruses. However, small sample sizes and a lack of standardized protocols can introduce interlaboratory variability, complicating interpretation of transmission experimental data. To assess the range of variation in ferret transmission experiments, a global exercise was conducted by 11 laboratories using two common stock H1N1 influenza viruses with different transmission characteristics in ferrets. Parameters known to affect transmission were standardized, including the inoculation route, dose, and volume, as well as a strict 1:1 donor/contact ratio for respiratory droplet transmission. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored and analyzed. The overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. Among environmental parameters that varied across laboratories, donor-to-contact airflow directionality was associated with increased transmissibility. To attain high confidence in identifying viruses with moderate to high transmissibility or low transmissibility under a smaller number of participating laboratories, our analyses support the notion that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment. IMPORTANCE Following detection of a novel virus, rapid characterization efforts (both in vitro and in vivo) are undertaken at numerous laboratories worldwide to evaluate the relative risk posed to human health. Aggregation of these data are critical, but the use of nonstandardized protocols can make interpretation of divergent results a challenge. For evaluation of virus transmissibility, a multifactorial trait which can only be evaluated in vivo, identifying intrinsic levels of variability between groups can improve the utility of these data, as well as ensure that experiments are performed with sufficient replication to ensure high confidence in compiled results. Using the ferret transmission model and two influenza A viruses, we conducted a multicenter standardization exercise to improve the interpretation of transmission data generated during risk assessment activities; this exercise serves as a model for future efforts employing both in vitro and in vivo models against possible pandemic pathogens. |
Neonatal jaundice: Knowledge and practices of healthcare providers and trainees in Southwest Nigeria
Barclay E , Ojo I , Hake A , Oyenuga A , Satrom K , Lund T , Oyenuga M , Slusher T , Gbadero D . Am J Trop Med Hyg 2022 107 (2) 328-35 Severe neonatal jaundice (SNNJ) is a leading cause of neonatal morbidity and mortality in low- and middle-income countries (LMICs). Risk mitigation and management modalities for SNNJ have led to a marked reduction in complications in high-income countries but not in LMICs likely in part due to knowledge gaps among healthcare providers. This study, a cross-sectional study conducted in Ogbomosho, Nigeria, aimed to identify SNNJ knowledge and practices among Nigerian healthcare providers/trainees. Healthcare providers/trainees completed a structured questionnaire. Healthcare providers/trainees included are nurse midwives (33.4%), nurses (18.6%), nursing students (15.2%), traditional birth attendants (TBAs) (12.7%), physicians (10.2%), and medical students (9.9%). Most physicians were aware of the common causes of SNNJ; however, knowledge deficits in other groups were notable. Despite most providers endorsing that glucose-6-phosphate dehydrogenase deficiency can cause SNNJ (91% of physicians, 60% of nurses, 71% of midwives, 81% of medical students, 43% of nursing students, 7% of TBAs), very few providers recognized that it is common, ranging from 3% in nurses up to a high of 47% among medical students. Gaps in provider knowledge regarding preventative measures and sequela were also noted. These data identified significant knowledge gaps regarding the etiology of SNNJ among healthcare providers/trainees, which can lead to missed opportunities in effective prevention and treatment. These deficits must be addressed if we are to eliminate tragic and preventable complications from SNNJ in Nigeria and other LMICs. |
Spatiotemporal trends in norovirus outbreaks in the United States, 2009-2019
Kambhampati AK , Calderwood L , Wikswo ME , Barclay L , Mattison CP , Balachandran N , Vinjé J , Hall AJ , Mirza SA . Clin Infect Dis 2022 76 (4) 667-673 BACKGROUND: Globally, noroviruses cause infections year-round but have recognized winter seasonality in the northern hemisphere and yearly variations in incidence. With candidate norovirus vaccines in development, understanding temporal and geographic trends in norovirus disease is important to inform potential vaccination strategies and evaluate vaccine impact. METHODS: We analyzed data from the National Outbreak Reporting System (NORS) and CaliciNet on single-state norovirus outbreaks that occurred from August 2009-July 2019 in the contiguous United States. We defined norovirus season onset and offset as the weeks by which 10% and 90% of norovirus outbreaks in a surveillance year occurred, respectively, and duration as the difference in weeks between onset and offset. We compared norovirus seasons across surveillance years and geographic regions. RESULTS: During August 2009-July 2019, 24,995 single-state norovirus outbreaks were reported to NORS and/or CaliciNet. Nationally, median norovirus season duration was 24 weeks, with onset occurring between October-December and offset occurring between April-May. Across all years combined, we observed a west-to-east trend in seasonality, with the earliest onset (October) and latest offset (May) occurring in western regions and the latest onset (December) and earliest offset (April) occurring in northeastern regions. CONCLUSIONS: Timing and duration of the US norovirus season varied annually, but generally occurred during October-May. Norovirus wintertime seasonality was less distinct in western regions and was progressively more pronounced moving east. Further understanding the drivers of spatiotemporal dynamics of norovirus could provide insights into factors promoting virus transmission and help guide future interventions. |
Norovirus outbreaks in long-term care facilities in the United States, 2009-2018: a decade of surveillance
Calderwood LE , Wikswo ME , Mattison CP , Kambhampati AK , Balachandran N , Vinjé J , Barclay L , Hall AJ , Parashar U , Mirza SA . Clin Infect Dis 2021 74 (1) 113-119 BACKGROUND: In the US, norovirus is the leading cause of healthcare-associated gastroenteritis outbreaks. To inform prevention efforts, we describe the epidemiology of norovirus outbreaks in long-term care facilities (LTCFs). METHODS: CDC collects epidemiologic and laboratory data on norovirus outbreaks from U.S. health departments through the National Outbreak Reporting System (NORS) and CaliciNet. Reports from both systems were merged, and norovirus outbreaks in nursing homes, assisted living, and other LTCFs occurring in 2009-2018 were analyzed. Data from the Centers for Medicare and Medicaid Services and the National Center for Health Statistics were used to estimate state LTCF counts. RESULTS: During 2009-2018, 50 states, Washington D.C., and Puerto Rico reported 13,092 norovirus outbreaks and 416,284 outbreak-associated cases in LTCFs. Participation in NORS and CaliciNet increased from 2009-2014 and median reporting of LTCF norovirus outbreaks stabilized at 4.1 outbreaks per 100 LTCFs (IQR: 1.0-7.1) annually since 2014. Most outbreaks were spread via person-to-person transmission (90.4%) and 75% occurred during December-March. Genogroup was reported for 7,292 outbreaks with 862 (11.8%) positive for GI and 6,370 (87.3%) for GII. Among 4,425 GII outbreaks with typing data, 3,618 (81.8%) were GII.4. LTCF residents had higher attack rates than staff (median 29.0% versus 10.9%; p<0.001). For every 1,000 cases, there were 21.6 hospitalizations and 2.3 deaths. CONCLUSIONS: LTCFs have a high burden of norovirus outbreaks. Most LTCF norovirus outbreaks occurred during winter months and were spread person-to-person. Outbreak surveillance can inform development of interventions for this vulnerable population, such as vaccines targeting GII.4 norovirus strains. |
Detection of SARS-CoV-2 on Surfaces in Households of Persons with COVID-19.
Marcenac P , Park GW , Duca LM , Lewis NM , Dietrich EA , Barclay L , Tamin A , Harcourt JL , Thornburg NJ , Rispens J , Matanock A , Kiphibane T , Christensen K , Pawloski LC , Fry AM , Hall AJ , Tate JE , Vinjé J , Kirking HL , Pevzner E . Int J Environ Res Public Health 2021 18 (15) SARS-CoV-2 transmission from contaminated surfaces, or fomites, has been a concern during the COVID-19 pandemic. Households have been important sites of transmission throughout the COVID-19 pandemic, but there is limited information on SARS-CoV-2 contamination of surfaces in these settings. We describe environmental detection of SARS-CoV-2 in households of persons with COVID-19 to better characterize the potential risks of fomite transmission. Ten households with ≥1 person with laboratory-confirmed COVID-19 and with ≥2 members total were enrolled in Utah, U.S.A. Nasopharyngeal and anterior nasal swabs were collected from members and tested for the presence of SARS-CoV-2 by RT-PCR. Fifteen surfaces were sampled in each household and tested for presence and viability of SARS-CoV-2. SARS-CoV-2 RNA was detected in 23 (15%) of 150 environmental swab samples, most frequently on nightstands (4/6; 67%), pillows (4/23; 17%), and light switches (3/21; 14%). Viable SARS-CoV-2 was cultured from one sample. All households with SARS-CoV-2-positive surfaces had ≥1 person who first tested positive for SARS-CoV-2 ≤ 6 days prior to environmental sampling. SARS-CoV-2 surface contamination occurred early in the course of infection when respiratory transmission is most likely, notably on surfaces in close, prolonged contact with persons with COVID-19. While fomite transmission might be possible, risk is low. |
Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritis.
Cannon JL , Bonifacio J , Bucardo F , Buesa J , Bruggink L , Chan MC , Fumian TM , Giri S , Gonzalez MD , Hewitt J , Lin JH , Mans J , Muñoz C , Pan CY , Pang XL , Pietsch C , Rahman M , Sakon N , Selvarangan R , Browne H , Barclay L , Vinjé J . Emerg Infect Dis 2021 27 (5) 1438-1445 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. |
Burden and etiology of moderate and severe diarrhea in children less than 5years of age living in north and south of China: Prospective, population-based surveillance
Zhou HL , Bessey T , Wang SM , Mo ZJ , Barclay L , Wang JX , Zhang CJ , Ma JC , Qiu C , Zhao G , Li RC , Zhao YL , Jiang B , Wang XY . Gut Pathog 2021 13 (1) 33 BACKGROUND: Diarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures. METHODS: Population-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter. Stool specimens were collected from children < 5 years of age experiencing diarrhea. The TaqMan Array Card (TAC), based on multiplex real-time PCR, was applied to detect multiple enteric microbial agents simultaneously. Results using these methods were compared to those derived from conventional PCR assays. RESULTS: During the study period, 6,380 children in Zhengding and 3,581 children in Sanjiang < 5 years of age participated. Three hundred and forty (31.2%) and 279 (22.9%) diarrhea episodes were identified as moderate-to-severe in the two counties, with incidence of 60.4 and 88.3 cases per 1,000 child-years in Zhengding and Sanjiang, respectively. The five most frequently detected bacterial and viral agents in Sanjiang were adenovirus, enterovirus, enteroaggregative Escherichia coli (EAEC), rotavirus, and sapovirus all the year round, while the most common viral agents in Zhengding were rotavirus, followed by astrovirus and adenovirus during the cool season. Compared to conventional PCR assay, the average incremental detection via the TAC method was twofold. CONCLUSION: Our study demonstrated high diversity and prevalence of multiple major bacterial and viral agents, including rotavirus and calicivirus, among children in China. Further studies are needed to define the public health significance of neglected but frequently detected pathogens such as EAEC, enterotoxigenic E. coli, Campylobacter, adenovirus, and enterovirus. |
Rare Norovirus GIV Foodborne Outbreak, Wisconsin, USA
Barclay L , Davis T , Vinjé J . Emerg Infect Dis 2021 27 (4) 1151-1154 We report a norovirus GIV outbreak in the United States, 15 years after the last reported outbreak. During May 2016 in Wisconsin, 53 persons, including 4 food handlers, reported being ill. The outbreak was linked to individually prepared fruit consumed as a fruit salad. The virus was phylogenetically classified as a novel GIV genotype. |
Human Calicivirus Typing tool: A web-based tool for genotyping human norovirus and sapovirus sequences.
Tatusov RL , Chhabra P , Diez-Valcarce M , Barclay L , Cannon JL , Vinjé J . J Clin Virol 2020 134 104718 BACKGROUND: The family Caliciviridae consists of a genetically diverse group of RNA viruses that infect a wide range of host species including noroviruses and sapoviruses which cause acute gastroenteritis in humans. Typing of these viruses relies on sequence-based approaches, and therefore there is a need for rapid and accurate web-based typing tools. OBJECTIVE: To develop and evaluate a web-based tool for rapid and accurate genotyping of noroviruses and sapoviruses. METHODS: The Human Calicivirus Typing (HuCaT) tool uses a set of curated reference sequences that are compared to query sequences using a k-mer (DNA substring) based algorithm. Outputs include alignments and phylogenetic trees of the 12 top matching reference sequences for each query. RESULTS: The HuCaT tool was validated with a set of 1310 norovirus and 239 sapovirus sequences covering all known human norovirus and sapovirus genotypes. HuCaT tool assigned genotypes to all queries with 100 % accuracy and was much faster (17 s) than BLAST (150 s) or phylogenetic analyses approaches. CONCLUSIONS: The web-based HuCaT tool supports rapid and accurate genotyping of human noroviruses and sapoviruses. |
Single-step RT-PCR assay for dual genotyping of GI and GII norovirus strains.
Chhabra P , Browne H , Huynh T , Diez-Valcarce M , Barclay L , Kosek MN , Ahmed T , Lopez MR , Pan CY , Vinjé J . J Clin Virol 2020 134 104689 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. |
Identifying septic pollution exposure routes during a waterborne norovirus outbreak - A new application for human-associated microbial source tracking qPCR.
Mattioli MC , Benedict KM , Murphy J , Kahler A , Kline KE , Longenberger A , Mitchell PK , Watkins S , Berger P , Shanks OC , Barrett CE , Barclay L , Hall AJ , Hill V , Weltman A . J Microbiol Methods 2020 180 106091 In June 2017, the Pennsylvania Department of Health (PADOH) was notified of multiple norovirus outbreaks associated with 179 ill individuals who attended separate events held at an outdoor venue and campground over a month period. Epidemiologic investigations were unable to identify a single exposure route and therefore unable to determine whether there was a persistent contamination source to target for exposure mitigation. Norovirus was detected in a fresh recreational water designated swimming area and a drinking water well. A hydrogeological site evaluation suggested a nearby septic leach field as a potential contamination source via ground water infiltration. Geological characterization revealed a steep dip of the bedrock beneath the septic leach field toward the well, providing a viral transport pathway in a geologic medium not previously documented as high risk for viral ground water contamination. The human-associated microbial source tracking (MST) genetic marker, HF183, was used as a microbial tracer to demonstrate the hydrogeological connection between the malfunctioning septic system, drinking water well, and recreational water area. Based on environmental investigation findings, venue management and local public health officials implemented a series of outbreak prevention strategies including discontinuing the use of the contaminated well, issuing a permit for a new drinking water well, increasing portable toilet and handwashing station availability, and promoting proper hand hygiene. Despite the outbreaks at the venue and evidence of ground water contamination impacting nearby recreational water and the drinking water well, no new norovirus cases were reported during a large event one week after implementing prevention practices. This investigation highlights a new application for human-associated MST methods to trace hydrological connections between multiple fecal pollutant exposure routes in an outbreak scenario. In turn, pollutant source information can be used to develop effective intervention practices to mitigate exposure and prevent future outbreaks associated with human fecal contaminated waters. |
Notes from the field: Multiple cruise ship outbreaks of norovirus associated with frozen fruits and berries - United States, 2019
Rispens JR , Freeland A , Wittry B , Kramer A , Barclay L , Vinje J , Treffiletti A , Houston K . MMWR Morb Mortal Wkly Rep 2020 69 (16) 501-502 From July to September 2019, cruise line X experienced sudden, unexplained outbreaks (>3% of the passenger population) of acute gastroenteritis (AGE) among passengers on 10 cruise ships sailing in Europe. The rapid onset of vomiting and diarrhea followed by recovery within 24 hours were consistent with norovirus infection. Investigations by the cruise line throughout the summer yielded no clear source of the outbreaks even after extensive food testing. On September 18, 2019, CDC’s Vessel Sanitation Program (VSP) was notified of an outbreak of AGE on cruise ship A of cruise line X, sailing into U.S. jurisdiction (defined as passenger vessels carrying ≥13 passengers sailing to the United States from a foreign port) from Germany to New York City (1). By the end of the 19-day voyage on September 23, a total of 117 of 2,046 (5.7%) passengers and eight of 610 (1.3%) crew members met the case definition for AGE (three or more loose stools within a 24-hour period or more than normal for the patient, or vomiting plus one other sign or symptom including fever, diarrhea, bloody stool, myalgia, abdominal cramps, or headache). Four stool specimens were collected and tested for norovirus at CDC’s National Calicivirus Laboratory; three tested positive for norovirus by quantitative reverse transcription–polymerase chain reaction (RT-PCR). No outbreak source was determined after a field investigation by a VSP team on September 22. |
Molecular Epidemiology of Norovirus Outbreaks in Argentina, 2013-2018.
Degiuseppe JI , Barclay L , Gomes KA , Costantini V , Vinje J , Stupka JA . J Med Virol 2020 92 (8) 1330-1333 Noroviruses are a leading cause of endemic and epidemic acute gastroenteritis in all age groups. However, in Latin America there are limited and updated data regarding circulating genotypes. The aim of this study was to assess the prevalence and genetic diversity of norovirus outbreaks in Argentina from 2013-2018. Stool samples from 29 AGE outbreaks were available for viral testing. Norovirus was detected in samples from 18 (62.1%) outbreaks (2 GI and 16 GII). Both GI outbreaks were typed as GI.6[P11] whereas 10 different GII genotypes were detected, in which GII.4 viruses were the most frequently detected (29.4%, associated with GII.P31 and GII.P16) followed by GII.1[P33] and GII.6[P7] (17.6% each). Like GII.4 viruses, GII.2 viruses were also detected in association with different polymerases (GII.P2 and GII.P16). Our findings underscore the importance of dual RdRp-VP1 typing since recombinant strains with new polymerase sequences emerge frequently suggesting a possible role in improved fitness of these viruses. This study represents the most recent multi-year assessment of the molecular epidemiology of norovirus strains associated with AGE outbreaks in Argentina. Molecular surveillance of norovirus has to be considered to monitor possible changes in dominant genotypes which may assist to inform the formulation of future vaccines. This article is protected by copyright. All rights reserved. |
Emerging Novel GII.P16 Noroviruses Associated with Multiple Capsid Genotypes.
Barclay L , Cannon JL , Wikswo ME , Phillips AR , Browne H , Montmayeur AM , Tatusov RL , Burke RM , Hall AJ , Vinje J . Viruses 2019 11 (6) Noroviruses evolve by antigenic drift and recombination, which occurs most frequently at the junction between the non-structural and structural protein coding genomic regions. In 2015, a novel GII.P16-GII.4 Sydney recombinant strain emerged, replacing the predominance of GII.Pe-GII.4 Sydney among US outbreaks. Distinct from GII.P16 polymerases detected since 2010, this novel GII.P16 was subsequently detected among GII.1, GII.2, GII.3, GII.10 and GII.12 viruses, prompting an investigation on the unique characteristics of these viruses. Norovirus positive samples (n = 1807) were dual-typed, of which a subset (n = 124) was sequenced to yield near-complete genomes. CaliciNet and National Outbreak Reporting System (NORS) records were matched to link outbreak characteristics and case outcomes to molecular data and GenBank was mined for contextualization. Recombination with the novel GII.P16 polymerase extended GII.4 Sydney predominance and increased the number of GII.2 outbreaks in the US. Introduction of the novel GII.P16 noroviruses occurred without unique amino acid changes in VP1, more severe case outcomes, or differences in affected population. However, unique changes were found among NS1/2, NS4 and VP2 proteins, which have immune antagonistic functions, and the RdRp. Multiple polymerase-capsid combinations were detected among GII viruses including 11 involving GII.P16. Molecular surveillance of protein sequences from norovirus genomes can inform the functional importance of amino acid changes in emerging recombinant viruses and aid in vaccine and antiviral formulation. |
Impact of long-term storage of clinical samples collected from 1996 to 2017 on RT-PCR detection of norovirus.
Cannon JL , Baker M , Barclay L , Vinje J . J Virol Methods 2019 267 35-41 Noroviruses are recognized as the leading cause of acute gastroenteritis globally. With improved molecular diagnostics developed over the last two decades, archived clinical specimens are increasingly used to investigate the historic prevalence and molecular epidemiology of human norovirus. Yet the impact of long-term storage on viral integrity in clinical specimens has not been evaluated. In this study, we retested 994 stool specimens collected between 1996 and 2017 that originally tested norovirus-positive to quantify the loss of norovirus RT-PCR positivity with increasing sample storage time at 4 degrees C. In all, 79% of samples tested positive after retesting, but there was an approximate 3% decline in the positivity ratio and 4% decline in the percentage of samples that could be genotyped with each additional year of sample storage. For samples that were originally quantified by real-time RT-PCR (collected between 2003-2017), there was an estimated 1-log loss of viral titer occurring every 7 years of sample storage. Few samples contained PCR inhibitors, assessed using a MS2 extraction control, indicating that loss of RT-PCR signal was due primarily to loss of viral RNA integrity after long-term storage of stool samples at 4 degrees C. Our results indicate that norovirus positive stool samples can be stored with minimal loss in RT-PCR positivity when stored less than a decade. Longer periods of storage may impair norovirus detection, potentially impacting historic estimates of norovirus prevalence and molecular epidemiology if derived by testing archival clinical specimens. |
The norovirus epidemiologic triad: Predictors of severe outcomes in US norovirus outbreaks, 2009-2016
Burke RM , Shah MP , Wikswo ME , Barclay L , Kambhampati A , Marsh Z , Cannon JL , Parashar UD , Vinje J , Hall AJ . J Infect Dis 2018 219 (9) 1364-1372 Background: Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. Clarifying the viral, host, and environmental factors (epidemiologic triad) associated with severe outcomes can help target public health interventions. Methods: Acute norovirus outbreaks reported to the National Outbreak Reporting System (NORS) in 2009-2016 were linked to laboratory-confirmed norovirus outbreaks reported to CaliciNet. Outbreaks were analyzed for differences in genotype (GII.4 vs non-GII.4), hospitalization, and mortality rates by timing, setting, transmission mode, demographics, clinical symptoms, and health outcomes. Results: A total of 3747 norovirus outbreaks were matched from NORS and CaliciNet. Multivariable models showed that GII.4 outbreaks (n = 2353) were associated with healthcare settings (odds ratio [OR], 3.94 [95% confidence interval {CI}, 2.99-5.23]), winter months (November-April; 1.55 [95% CI, 1.24-1.93]), and older age of cases (>/=50% aged >/=75 years; 1.37 [95% CI, 1.04-1.79]). Severe outcomes were more likely among GII.4 outbreaks (hospitalization rate ratio [RR], 1.54 [95% CI, 1.23-1.96]; mortality RR, 2.77 [95% CI, 1.04-5.78]). Outbreaks in healthcare settings were also associated with higher hospitalization (RR, 3.22 [95% CI, 2.34-4.44]) and mortality rates (RR, 5.65 [95% CI, 1.92-18.70]). Conclusions: Severe outcomes more frequently occurred in norovirus outbreaks caused by GII.4 and those in healthcare settings. These results should help guide preventive interventions for targeted populations, including vaccine development. |
Epidemiologic and Genotypic distribution of Noroviruses among children with Acute Diarrhea and Healthy Controls in a Low-income Rural Setting.
Hossain ME , Rahman R , Ali SI , Islam MM , Rahman MZ , Ahmed S , Faruque ASG , Barclay L , Vinje J , Rahman M . Clin Infect Dis 2018 69 (3) 505-513 Background: Noroviruses are the most common cause of epidemic and endemic acute gastroenteritis (AGE) worldwide. The burden of norovirus disease in low-income settings is poorly understood. Methods: We tested stool samples from children less than 5 years of age with diarrhea who were admitted in a rural hospital in Bangladesh from 2010-2012 and from matched healthy controls from the same catchment area. Results: Norovirus was detected in 109 (18%) of 613 children with diarrhea and in 30 (15%) of 206 healthy controls. Most (n=118; 85%) norovirus infections belonged to genogroup II (GII). Of these, GII.4 viruses were identified in 36 (33%) of the cases and in 6 (21%) of the controls. Other major genotypes included GII.3 (13%), GII.6 (11%), and GII.13 (11%) in cases and GII.6 (17%) and GII.2 (14%) in controls. Greatest risk of severe norovirus disease (Vesikari score >/=11) was associated to GII.4 infections. GII.4 viruses were the predominant genotype detected during the winter (55%) and rainy season (23%) while GII.3 (19%) and GII.13 (19%) viruses were the most prevalent genotypes during the summer. Vomiting was significantly associated with GII.4 infection, while longer duration of diarrhea with GI.3 infection. Conclusions: Future studies are needed to understand the high rates of virus shedding in children without AGE symptoms. |
Ferrets as models for influenza virus transmission studies and pandemic risk assessments
Belser JA , Barclay W , Barr I , Fouchier RAM , Matsuyama R , Nishiura H , Peiris M , Russell CJ , Subbarao K , Zhu H , Yen HL . Emerg Infect Dis 2018 24 (6) 965-971 The ferret transmission model is extensively used to assess the pandemic potential of emerging influenza viruses, yet experimental conditions and reported results vary among laboratories. Such variation can be a critical consideration when contextualizing results from independent risk-assessment studies of novel and emerging influenza viruses. To streamline interpretation of data generated in different laboratories, we provide a consensus on experimental parameters that define risk-assessment experiments of influenza virus transmissibility, including disclosure of variables known or suspected to contribute to experimental variability in this model, and advocate adoption of more standardized practices. We also discuss current limitations of the ferret transmission model and highlight continued refinements and advances to this model ongoing in laboratories. Understanding, disclosing, and standardizing the critical parameters of ferret transmission studies will improve the comparability and reproducibility of pandemic influenza risk assessment and increase the statistical power and, perhaps, accuracy of this model. |
Evaluation of RIDA ® GENE norovirus GI/GII real time RT-PCR using stool specimens collected from children and adults with acute gastroenteritis.
Kanwar N , Hassan F , Barclay L , Langley C , Vinje J , Bryant PW , George KS , Mosher L , Matthews-Greer JM , Rocha MA , Beenhouwer DO , Harrison CJ , Moffatt M , Shastri N , Selvarangan R . J Clin Virol 2018 104 1-4 BACKGROUND: Norovirus is the leading cause of epidemic and sporadic acute gastroenteritis (AGE) in the United States. Widespread prevalence necessitates implementation of accurate norovirus detection assays in clinical diagnostic laboratories. OBJECTIVE: To evaluate RIDA((R))GENE norovirus GI/GII real-time RT-PCR assay (RGN RT-PCR) using stool samples from patients with sporadic AGE. STUDY DESIGN: Patients between 14days to 101 years of age with symptoms of AGE were enrolled prospectively at four sites across the United States during 2014-2015. Stool specimens were screened for the presence of norovirus RNA by the RGN RT-PCR assay. Results were compared with a reference method that included conventional RT-PCR and sequencing of a partial region of the 5'end of the norovirus ORF2 gene. RESULTS: A total of 259 (36.0%) of 719 specimens tested positive for norovirus by the reference method. The RGN RT-PCR assay detected norovirus in 244 (94%) of these 259 norovirus positive specimens. The sensitivity and specificity (95% confidence interval) of the RGN RT-PCR assay for detecting norovirus genogroup (G) I was 82.8% (63.5-93.5) and 99.1% (98.0-99.6) and for GII was 94.8% (90.8-97.2) and 98.6% (96.9-99.4), respectively. Seven specimens tested positive by the RGN-RT PCR that were negative by the reference method. The fifteen false negative samples were typed as GII.4 Sydney, GII.13, GI.3, GI.5, GI.2, GII.1, and GII.3 in the reference method. CONCLUSIONS: The RGN RT-PCR assay had a high sensitivity and specificity for the detection of norovirus in stool specimens from patients with sporadic AGE. |
Can Use of Viral Load Improve Norovirus Clinical Diagnosis and Disease Attribution?
Shioda K , Barclay L , Becker-Dreps S , Bucardo-Rivera F , Cooper PJ , Payne DC , Vinjé J , Lopman BA . Open Forum Infect Dis 2017 4 (3) ofx131 BACKGROUND: Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) is the state-of-the-art diagnostic for norovirus. Cycle threshold (Ct), an indicator of viral load, may be associated with symptomatic disease as well as demographic and outbreak characteristics. METHODS: Data on (1) outbreak and sporadic cases and (2) asymptomatic controls in the United States and Latin America were analyzed. With multivariate regression models, we assessed relationships between various factors and Ct values, and we calculated odds ratios (ORs) for the presence of symptoms and attributable fractions of norovirus. Receiver-operating characteristic analysis was performed to define an optimal Ct cutoff to identify disease-causing infections. RESULTS: Cycle threshold values were lower (ie, higher viral loads) among symptomatic cases (model-adjusted mean ± standard error: 25.3 ± 1.2) compared with asymptomatic controls (28.5 ± 1.4). Cycle threshold values were significantly different across age groups, norovirus genogroups, timing of specimen collection, outbreak settings, and transmission modes. Genogroup II (GII) Ct values were associated with presence of symptoms (OR = 1.1), allowing us to estimate that 16% of diarrheal disease was attributable to norovirus. The optimized Ct cutoff led to poor sensitivity and specificity for genogroup I and GII. CONCLUSIONS: Cycle threshold values were associated with host, pathogen, and outbreak factors. Cycle threshold values may not effectively distinguish disease-causing infection for individual patients, but they are useful for epidemiological studies aiming to attribute disease. |
Genetic and Epidemiologic Trends of Norovirus Outbreaks in the US Demonstrated Emergence of Novel GII.4 Recombinant Viruses, 2013-2016.
Cannon JL , Barclay L , Collins NR , Wikswo ME , Castro CJ , Magana LC , Gregoricus N , Marine RL , Chhabra P , Vinje J . J Clin Microbiol 2017 55 (7) 2208-2221 Noroviruses are the most frequent cause of epidemic acute gastroenteritis in the United States (US). Between September 2013 and August 2016, 2,715 genotyped norovirus outbreaks were submitted to CaliciNet. GII.4 Sydney viruses caused 58% of outbreaks during these years. A GII.4 Sydney variant with a novel GII.P16 polymerase emerged in November 2015, causing 60% of all GII.4 outbreaks in the 2015-2016 season. Multiple polymerase types were found associated with GII.2 (3), GII.3 (3), GII.4 Sydney (3), GII.13 (2) and GII.17 (2) genotypes, 4 of which included GII.P16 variants. GII.P16 polymerase sequences associated with GII.2 and GII.4 Sydney strains were nearly identical, suggesting common ancestry. Other common genotypes, each causing 5-17% of outbreaks in a season, included GI.3, GI.5, GII.2, GII.3, GII.6, GII.13 and GII.17 Kawasaki. Acquisition of alternative RNA polymerases by recombination is an important mechanism for norovirus evolution and a phenomenon that was shown to occur more frequently than previously recognized in the US. Continued molecular surveillance of norovirus strains, including typing of both polymerase and capsid genes, is important for monitoring emerging strains in our continued efforts to reduce the overall burden of norovirus disease. |
Near Real-Time Surveillance of U.S. Norovirus Outbreaks by the Norovirus Sentinel Testing and Tracking Network - United States, August 2009-July 2015.
Shah MP , Wikswo ME , Barclay L , Kambhampati A , Shioda K , Parashar UD , Vinje J , Hall AJ . MMWR Morb Mortal Wkly Rep 2017 66 (7) 185-189 Norovirus is the leading cause of endemic and epidemic acute gastroenteritis in the United States. New variant strains of norovirus GII.4 emerge every 2-4 years and are often associated with increased disease and health care visits. Since 2009, CDC has obtained epidemiologic data on norovirus outbreaks from state health departments through the National Outbreak Reporting System (NORS) and laboratory data through CaliciNet. NORS is a web-based platform for reporting waterborne, foodborne, and enteric disease outbreaks of all etiologies, including norovirus, to CDC. CaliciNet, a nationwide electronic surveillance system of local and state public health and regulatory agency laboratories, collects genetic sequences of norovirus strains associated with gastroenteritis outbreaks. Because these two independent reporting systems contain complementary data, integration of NORS and CaliciNet records could provide valuable public health information about norovirus outbreaks. However, reporting lags and inconsistent identification codes in NORS and CaliciNet records have been an obstacle to developing an integrated surveillance system. |
Viral factors in influenza pandemic risk assessment.
Lipsitch M , Barclay W , Raman R , Russell CJ , Belser JA , Cobey S , Kasson PM , Lloyd-Smith JO , Maurer-Stroh S , Riley S , Beauchemin CA , Bedford T , Friedrich TC , Handel A , Herfst S , Murcia PR , Roche B , Wilke CO , Russell CA . Elife 2016 5 The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk. |
Strain-Specific Virolysis Patterns of Human Noroviruses in Response to Alcohols.
Park GW , Collins N , Barclay L , Hu L , Prasad BV , Lopman BA , Vinje J . PLoS One 2016 11 (6) e0157787 Alcohol-based hand sanitizers are widely used to disinfect hands to prevent the spread of pathogens including noroviruses. Alcohols inactivate norovirus by destruction of the viral capsid, resulting in the leakage of viral RNA (virolysis). Since conflicting results have been reported on the susceptibility of human noroviruses against alcohols, we exposed a panel of 30 human norovirus strains (14 GI and 16 GII strains) to different concentrations (50%, 70%, 90%) of ethanol and isopropanol and tested the viral RNA titer by RT-qPCR. Viral RNA titers of 10 (71.4%), 14 (100%), 3 (21.4%) and 7 (50%) of the 14 GI strains were reduced by > 1 log10 RNA copies/ml after exposure to 70% and 90% ethanol, and 70% and 90% isopropanol, respectively. RNA titers of 6 of the 7 non-GII 4 strains remained unaffected after alcohol exposure. Compared to GII strains, GI strains were more susceptible to ethanol than to isopropanol. At 90%, both alcohols reduced RNA titers of 8 of the 9 GII.4 strains by ≥ 1 log10 RNA copies/ml. After exposure to 70% ethanol, RNA titers of GII.4 Den Haag and Sydney strains decreased by ≥ 1.9 log10, whereas RNA reductions for GII.4 New Orleans strains were < 0.5 log10. To explain these differences, we sequenced the complete capsid gene of the 9 GII.4 strains and identified 17 amino acid substitutions in the P2 region among the 3 GII.4 variant viruses. When comparing with an additional set of 200 GII.4 VP1 sequences, only S310 and P396 were present in all GII.4 New Orleans viruses but not in the ethanol-sensitive GII.4 Sydney and GII.4 Den Haag viruses Our data demonstrate that alcohol susceptibility patterns between different norovirus genotypes vary widely and that virolysis data for a single strain or genotype are not representative for all noroviruses. |
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