Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-25 (of 25 Records) |
Query Trace: Chhabra P[original query] |
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Traceback and testing of food epidemiologically linked to a norovirus outbreak at a wedding reception
Papafragkou E , Kita-Yarbro A , Yang Z , Chhabra P , Davis T , Blackmore J , Ziemer C , Klos R , Hall AJ , Vinjé J . J Food Prot 2024 100395 ![]() ![]() We investigated a suspected norovirus outbreak associated with a wedding reception in Wisconsin in May 2015. Fifty-six of 106 (53%) wedding attendees were interviewed and 23 (41%) reported symptoms consistent with norovirus infection. A retrospective cohort study identified fruit salad as the likely vehicle of infection (risk ratio 3.2, 95% confidence interval 1.1- 8.3). Norovirus was detected by real-time reverse transcription polymerase chain reaction (RT-qPCR) in stool specimens collected from four attendees and one food handler and in 12 leftover fruit salad samples from both an opened and a sealed container. Norovirus-positive clinical samples (n=4) were genotyped as GII.4 Sydney and norovirus-positive fruit salad samples (n=2) confirmed the presence of GII.4 norovirus by Sanger sequencing with 98% nucleotide (n=236) similarity in 5' end of ORF2 between fruit salad and clinical specimens. In conclusion, this comprehensive norovirus outbreak investigation combined epidemiologic, virologic, and environmental findings to traceback the contaminated food as the source of the outbreak. |
Increased circulation of GII.17 noroviruses, six European countries and the United States, 2023 to 2024
Chhabra P , Wong S , Niendorf S , Lederer I , Vennema H , Faber M , Nisavanh A , Jacobsen S , Williams R , Colgan A , Yandle Z , Garvey P , Al-Hello H , Ambert-Balay K , Barclay L , de Graaf M , Celma C , Breuer J , Vinjé J , Douglas A . Euro Surveill 2024 29 (39) ![]() We report an increase in GII.17 norovirus outbreaks and sporadic infections of acute gastroenteritis in Austria, Germany, France, Ireland, the Netherlands, England and the United States during the 2023/24 season. A decrease in GII.4 coincided with GII.17 prevalence increasing to between 17% and 64% of all GII detections. Overall, 84% of the GII.17 strains clustered closely with strains first reported in Romania in 2021 and two new sub-lineages were identified. Norovirus surveillance and molecular characterisation should be prioritised this winter. |
Hospital-based norovirus surveillance in children <5 years of age from 2017 to 2019 in India
Giri S , Chhabra P , Kulkarni R , Reju S , Sabapathy SK , Selvarajan S , Varghese T , Kalaivanan M , Dorairaj P , Kalrao V , Mankar S , Sangamnerkar M , Chethrapilly Purushothaman GK , Srikanth P , Kang G , Vinjé J . J Med Virol 2024 96 (1) e29384 ![]() After the introduction of the rotavirus vaccine into the Universal Immunization Program in India in 2016, relatively few studies have assessed the prevalence and epidemiological patterns of acute gastroenteritis (AGE) among hospitalized children ≤5 years of age. We used a uniform protocol to recruit children with AGE as well as standardized testing and typing protocols. Stool specimens from children with AGE younger than 5 years of age admitted to six hospitals in three cities in India were collected from January 2017 through December 2019. Norovirus was detected by real-time reverse transcription-polymerase chain reaction (RT-qPCR) followed by typing positive specimens by conventional RT-PCR and Sanger sequencing. Norovirus was detected in 322 (14.8%) of 2182 specimens with the highest rate in 2018 (17.6%, 146/829), followed by 2019 (14.4%, 122/849) and 2017 (10.7%, 54/504). Rotavirus vaccine status was known for 91.6% of the children of which 70.4% were vaccinated and 29.6% not. Norovirus positivity in rotavirus-vaccinated children was 16.3% and 12% in unvaccinated children. GII.4 Sydney[P16] (39.3%), GII.4 Sydney[P31] (18.7%), GII.2[P16] (10%), GI.3[P13] (6.8%), GII.3[P16] (5.9%), and GII.13[P16] (5%) accounted for 85.8% (188/219) of the typed strains. Our data highlight the importance of norovirus in Indian children hospitalized with AGE. |
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. |
Paediatric acute hepatitis of unknown aetiology: a national surveillance investigation in the USA during 2021 and 2022
Cates J , Baker JM , Almendares O , Balachandran N , McKeever ER , Kambhampati AK , Cubenas C , Vinjé J , Cannon JL , Chhabra P , Freeman B , Reagan-Steiner S , Bhatnagar J , Gastañaduy PA , Kirking HL , Sugerman D , Parashar UD , Tate JE . Lancet Child Adolesc Health 2023 7 (11) 773-785 BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None. |
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. |
Adeno-associated virus type 2 in US children with acute severe hepatitis.
Servellita V , Gonzalez AS , Lamson DM , Foresythe A , Huh HJ , Bazinet AL , Bergman NH , Bull RL , Garcia KY , Goodrich JS , Lovett SP , Parker K , Radune D , Hatada A , Pan CY , Rizzo K , Bertumen JB , Morales C , Oluniyi PE , Nguyen J , Tan J , Stryke D , Jaber R , Leslie MT , Lyons Z , Hedman HD , Parashar U , Sullivan M , Wroblewski K , Oberste MS , Tate JE , Baker JM , Sugerman D , Potts C , Lu X , Chhabra P , Pediatric Hepatitis of Unknown Etiology Working Group , Ingram LA , Shiau H , Britt W , Sanchez LHG , Ciric C , Rostad CA , Vinjé J , Kirking HL , Wadford DA , Raborn RT , St George K , Chiu CY . Nature 2023 ![]() As of August 2022, clusters of acute severe hepatitis of unknown etiology in children have been reported from 35 countries, including the United States(1,2). Previous studies have found human adenoviruses (HAdVs) in the blood from cases in Europe and the United States(3-7), although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment based sequencing, and agnostic metagenomic sequencing to analyze samples from 16 HAdV-positive cases from October 1, 2021 to May 22, 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus 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 etiology (P<0.001). In controls, HAdV-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 (EBV), human herpesvirus 6 (HHV-6), and/or enterovirus A71 (EV-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. |
Corrigendum: Updated classification of norovirus genogroups and genotypes.
Chhabra P , Graaf M , Parra GI , Chan MC , Green K , Martella V , Wang Q , White PA , Katayama K , Vennema H , Koopmans MPG , Vinjé J . J Gen Virol 2020 101 (8) 893 ![]() The genotypes referred to in this article were stated incorrectly. The genotype number 49 should have been stated as 48 and the number 27 should have been stated as 26. These errors occurred in the 'Abstract' section on page 1, in the ‘Discussion’ section on page 11, and within Fig. 5 on page 12. | | The sentence in the 'Abstract' should have read: | | ‘Using previously described 2× standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 48 (9 GI, 26 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX).’ | | The sentence in the 'Discussion' section on page 11 should have read: | | ‘Viruses in these ten genogroups can be further divided into 48 confirmed capsid genotypes based on amino acids of the complete VP1 and 60 confirmed P-types based on partial nucleotide sequences of RdRp regions.’ | | Fig. 5 on page 12 erroneously stated ‘27+2T’. This should have been stated as ‘26+2T’. |
Advances in understanding of the innate immune response to human norovirus infection using organoid models.
Mboko WP , Chhabra P , Valcarce MD , Costantini V , Vinj J . J Gen Virol 2022 103 (1) ![]() ![]() Norovirus is the leading cause of epidemic and endemic acute gastroenteritis worldwide and the most frequent cause of foodborne illness in the United States. There is no specific treatment for norovirus infections and therapeutic interventions are based on alleviating symptoms and limiting viral transmission. The immune response to norovirus is not completely understood and mechanistic studies have been hindered by lack of a robust cell culture system. In recent years, the human intestinal enteroid/human intestinal organoid system (HIE/HIO) has enabled successful human norovirus replication. Cells derived from HIE have also successfully been subjected to genetic manipulation using viral vectors as well as CRISPR/Cas9 technology, thereby allowing studies to identify antiviral signaling pathways important in controlling norovirus infection. RNA sequencing using HIE cells has been used to investigate the transcriptional landscape during norovirus infection and to identify antiviral genes important in infection. Other cell culture platforms such as the microfluidics-based gut-on-chip technology in combination with the HIE/HIO system also have the potential to address fundamental questions on innate immunity to human norovirus. In this review, we highlight the recent advances in understanding the innate immune response to human norovirus infections in the HIE system, including the application of advanced molecular technologies that have become available in recent years such as the CRISPR/Cas9 and RNA sequencing, as well as the potential application of single cell transcriptomics, viral proteomics, and gut-on-a-chip technology to further elucidate innate immunity to norovirus. |
Detection of norovirus variant GII.4 Hong Kong in Asia and Europe, 2017-2019
Chan MC , Roy S , Bonifacio J , Zhang LY , Chhabra P , Chan JCM , Celma C , Igoy MA , Lau SL , Mohammad KN , Vinjé J , Vennema H , Breuer J , Koopmans M , de Graaf M . Emerg Infect Dis 2021 27 (1) 289-293 We report a new norovirus GII.4 variant, GII.4 Hong Kong, with low-level circulation in 4 Eurasia countries since mid-2017. Amino acid substitutions in key residues on the virus capsid associated with the emergence of pandemic noroviruses suggest that GII.4 Hong Kong has the potential to become the next pandemic variant. |
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. |
Homotypic and Heterotypic Protection and Risk of Reinfection Following Natural Norovirus Infection in a Highly Endemic Setting.
Chhabra P , Rouhani S , Browne H , Yori PP , Salas MS , Olortegui MP , Moulton LH , Kosek MN , Vinje J . Clin Infect Dis 2021 72 (2) 222-229 ![]() ![]() BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide yet there is limited information on homotypic or heterotypic protection following natural infection to guide vaccine development. METHODS: A total of 6,020 stools collected from 299 Peruvian children between 2010 and 2014 were tested by norovirus real-time RT-PCR followed by sequence-based genotyping. Cox proportional hazards models were used to derive adjusted hazard ratios (HR) of infection among children with versus without prior exposure. RESULTS: Norovirus was detected in 1,288 (21.3%) samples. GII.4 (26%), GII.6 (19%), and GI.3 (9%) viruses accounted for 54% of infections. Homotypic protection for GI.3 (HR=0.35; p=0.015), GI.7 (HR=0.19; p=0.022), GII.4 (HR=0.39; p<0.001), and GII.6 (HR=0.52; p=0.006) infections was observed. Hazard analysis showed that children with prior GII.4 infection exhibited heterotypic protection with a 48% reduction of subsequent GI.3 infection (HR=0.52; p=0.005). Prior exposure to GI.3, GII.2, and GII.17 infections enhanced susceptibility to subsequent infections with several other norovirus genotypes. CONCLUSIONS: Children up to 2 years of age infected with GII.4 noroviruses demonstrated both homotypic and heterotypic protection to re-infection with other genotypes. These data support the need for ongoing vaccine development efforts with GII.4 as the main component and caution the inclusion of genotypes that may enhance susceptibility to infections. |
Homotypic and heterotypic protection and risk of re-infection following natural norovirus infection in a highly endemic setting.
Chhabra P , Rouhani S , Browne H , Yori PP , Salas MS , Olortegui MP , Moulton LH , Kosek MN , Vinje J . Clin Infect Dis 2020 72 (2) 222-229 ![]() ![]() BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide yet there is limited information on homotypic or heterotypic protection following natural infection to guide vaccine development. METHODS: A total of 6,020 stools collected from 299 Peruvian children between 2010 and 2014 were tested by norovirus real-time RT-PCR followed by sequence-based genotyping. Cox proportional hazards models were used to derive adjusted hazard ratios (HR) of infection among children with versus without prior exposure. RESULTS: Norovirus was detected in 1,288 (21.3%) samples. GII.4 (26%), GII.6 (19%), and GI.3 (9%) viruses accounted for 54% of infections. Homotypic protection for GI.3 (HR=0.35; p=0.015), GI.7 (HR=0.19; p=0.022), GII.4 (HR=0.39; p<0.001), and GII.6 (HR=0.52; p=0.006) infections was observed. Hazard analysis showed that children with prior GII.4 infection exhibited heterotypic protection with a 48% reduction of subsequent GI.3 infection (HR=0.52; p=0.005). Prior exposure to GI.3, GII.2, and GII.17 infections enhanced susceptibility to subsequent infections with several other norovirus genotypes. CONCLUSIONS: Children up to 2 years of age infected with GII.4 noroviruses demonstrated both homotypic and heterotypic protection to re-infection with other genotypes. These data support the need for ongoing vaccine development efforts with GII.4 as the main component and caution the inclusion of genotypes that may enhance susceptibility to infections. |
Updated classification of norovirus genogroups and genotypes.
Chhabra P , de Graaf M , Parra GI , Chan MC , Green K , Martella V , Wang Q , White PA , Katayama K , Vennema H , Koopmans MPG , Vinje J . J Gen Virol 2019 100 (10) 1393-1406 ![]() ![]() Noroviruses are genetically diverse RNA viruses associated with acute gastroenteritis in mammalian hosts. Phylogenetically, they can be segregated into different genogroups as well as P (polymerase)-groups and further into genotypes and P-types based on amino acid diversity of the complete VP1 gene and nucleotide diversity of the RNA-dependent RNA polymerase (RdRp) region of ORF1, respectively. In recent years, several new noroviruses have been reported that warrant an update of the existing classification scheme. Using previously described 2x standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 49 (9 GI, 27 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX). Viruses for which currently only one sequence is available in public databases were classified into tentative new genogroups (GNA1 and GNA2) and genotypes (GII.NA1, GII.NA2 and GIV.NA1) with their definitive assignment awaiting additional related sequences. Based on nucleotide diversity in the RdRp region, noroviruses can be divided into 60 P-types (14 GI, 37 GII, 2 GIII, 1 GIV, 2 GV, 2 GVI, 1 GVII and 1 GX), 2 tentative P-groups and 14 tentative P-types. Future classification and nomenclature updates will be based on complete genome sequences and will be coordinated and disseminated by the international norovirus classification-working group. |
Genetic diversity of noroviruses circulating in a pediatric cohort in Bangladesh.
Nelson MI , Mahfuz M , Chhabra P , Haque R , Seidman JC , Hossain I , McGrath M , Ahmed AMS , Knobler S , Vinje J , Ahmed T . J Infect Dis 2018 218 (12) 1937-1942 ![]() ![]() Noroviruses are a leading cause of diarrhea in children <5yo worldwide. We genotyped 88 viruses collected by active surveillance in a birth cohort of children <2yo in Dhaka, Bangladesh, during 2010-2013. Twenty-five (81%) of 31 established GI and GII genotypes were detected, with GII.4 as the predominant genotype (20%). Our results show that children in Bangladesh are infected with a great diversity of norovirus strains. Re-infections are common, but not with closely related genotypes. Birth cohort studies are critical to understand cross-protective immunity and advance the development of pediatric norovirus vaccines. |
Near-Complete Genome Sequences of Several New Norovirus Genogroup II Genotypes.
Chhabra P , Aswath K , Collins N , Ahmed T , Olortegui MP , Kosek M , Cebelinski E , Cooper PJ , Bucardo F , Lopez MR , Castro CJ , Marine RL , Ng TFF , Vinje J . Genome Announc 2018 6 (6) ![]() We report here the near-complete genome sequences of 13 norovirus strains detected in stool samples from patients with acute gastroenteritis from Bangladesh, Ecuador, Guatemala, Peru, Nicaragua, and the United States that are classified into one existing (genotype II.22 [GII.22]), 3 novel (GII.23, GII.24 and GII.25), and 3 tentative novel (GII.NA1, GII.NA2, and GII.NA3) genotypes. |
Comparison of three multiplex gastrointestinal platforms for the detection of gastroenteritis viruses.
Chhabra P , Gregoricus N , Weinberg GA , Halasa N , Chappell J , Hassan F , Selvarangan R , Mijatovic-Rustempasic S , Ward ML , Bowen M , Payne DC , Vinje J . J Clin Virol 2017 95 66-71 ![]() BACKGROUND: Viruses are major etiological agents of childhood gastroenteritis. In recent years, several molecular platforms for the detection of viral enteric pathogens have become available. OBJECTIVE/STUDY DESIGN: We evaluated the performance of three multiplex platforms including Biofire's Gastrointestinal Panel (FilmArray), Luminex xTAG(R) Gastrointestinal Pathogen Panel (GPP), and the TaqMan Array Card (TAC) for the detection of five gastroenteritis viruses using a coded panel of 300 archived stool samples. RESULTS: The FilmArray detected a virus in 199 (96.1%) and the TAC in 172 (83.1%) of the 207 samples (187 samples positive for a single virus and 20 samples positive for more than one virus) whereas the GPP detected a virus in 100 (78.7%) of the 127 (97 positive for one virus and three positive for more than one virus) samples. Overall the clinical accuracy was highest for the FilmArray (98%) followed by TAC (97.2%) and GPP (96.9%). The sensitivity of the FilmArray, GPP and TAC platforms was highest for rotavirus (100%, 95.8%, and 89.6%, respectively) and lowest for adenovirus type 40/41 (97.4%, 57.9% and 68.4%). The specificity of the three platforms ranged from 95.6% (rotavirus) to 99.6% (norovirus/sapovirus) for the FilmArray, 99.6% (norovirus) to 100% (rotavirus/adenovirus) for GPP, and 98.9% (astrovirus) to 100% (rotavirus/sapovirus) for TAC. CONCLUSION: The FilmArray demonstrated the best analytical performance followed by TAC. In recent years, the availability of multi-enteric molecular testing platforms has increased significantly and our data highlight the strengths and weaknesses of these platforms. |
Critical role of RIG-I and MDA5 in early and late stages of Tulane virus infection.
Chhabra P , Ranjan P , Cromeans T , Sambhara S , Vinje J . J Gen Virol 2017 98 (5) 1016-1026 ![]() Human noroviruses are a major cause of acute gastroenteritis worldwide, but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus, Recovirus, in the family Caliciviridae. Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5). In this study, by using siRNA knockdown, we report that TV infection in LLC-MK2 cells results in an early [3 h post infection (h p.i.), P<0.05] RIG-I-dependent and type I interferon-mediated antiviral response, whereas an MDA5-mediated antiviral effect was observed at later (12 h p.i.; P<0.05) stages of TV replication. Induction of RIG-I and MDA5 was critical for inhibition of TV replication. Furthermore, pre-activation of the RIG-I/MDA5 pathway prevented TV replication (>900-fold decrease; P<0.05), suggesting that RIG-I and MDA5 ligands could be used to develop novel preventive and therapeutic measures against norovirus. |
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. |
Swab sampling method for the detection of human norovirus on surfaces
Park GW , Chhabra P , Vinje J . J Vis Exp 2017 (120) Human noroviruses are a leading cause of epidemic and sporadic gastroenteritis worldwide. Because most infections are either spread directly via the person-to-person route or indirectly through environmental surfaces or food, contaminated fomites and inanimate surfaces are important vehicles for the spread of the virus during norovirus outbreaks. We developed and evaluated a protocol using macrofoam swabs for the detection and typing of human noroviruses from hard surfaces. Compared with fiber-tipped swabs or antistatic wipes, macrofoam swabs allow virus recovery (range 1.2-33.6%) from toilet seat surfaces of up to 700 cm2. The protocol includes steps for the extraction of the virus from the swabs and further concentration of the viral RNA using spin columns. In total, 127 (58.5%) of 217 swab samples that had been collected from surfaces in cruise ships and long-term care facilities where norovirus gastroenteritis had been reported tested positive for GII norovirus by RT-qPCR. Of these 29 (22.8%) could be successfully genotyped. In conclusion, detection of norovirus on environmental surfaces using the protocol we developed may assist in determining the level of environmental contamination during outbreaks as well as detection of virus when clinical samples are not available; it may also facilitate monitoring of effectiveness of remediation strategies. |
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Shrivastava A , Kumar A , Thomas JD , Laserson KF , Bhushan G , Carter MD , Chhabra M , Mittal V , Khare S , Sejvar JJ , Dwivedi M , Isenberg SL , Johnson R , Pirkle JL , Sharer JD , Hall PL , Yadav R , Velayudhan A , Papanna M , Singh P , Somashekar D , Pradhan A , Goel K , Pandey R , Kumar M , Kumar S , Chakrabarti A , Sivaperumal P , Kumar AR , Schier JG , Chang A , Graham LA , Mathews TP , Johnson D , Valentin L , Caldwell KL , Jarrett JM , Harden LA , Takeoka GR , Tong S , Queen K , Paden C , Whitney A , Haberling DL , Singh R , Singh RS , Earhart KC , Dhariwal AC , Chauhan LS , Venkatesh S , Srikantiah P . Lancet Glob Health 2017 5 (4) e458-e466 BACKGROUND: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9.6 [95% CI 3.6 - 24]) and absence of an evening meal (2.2 [1.2-4.3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7.8 [95% CI 3.3-18.8], without evening meal; OR 3.6 [1.1-11.1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12.4 mug/g to 152.0 mug/g and MCPG ranged from 44.9 mug/g to 220.0 mug/g. INTERPRETATION: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING: US Centers for Disease Control and Prevention. |
Outbreaks of unexplained neurologic illness - Muzaffarpur, India, 2013-2014
Shrivastava A , Srikantiah P , Kumar A , Bhushan G , Goel K , Kumar S , Kumar T , Mohankumar R , Pandey R , Pathan P , Pappanna M , Pasi A , Pradhan A , Singh P , Somashekar D , Velayudhan A , Yadav R , Chhabra M , Mittal V , Khare S , Sejvar JJ , Dwivedi M , Laserson K , Earhart KC , Sivaperumal P , Kumar AR , Chakrabarti A , Thomas J , Schier J , Singh R , Singh RS , Dhariwal AC , Chauhan LS . MMWR Morb Mortal Wkly Rep 2015 64 (3) 49-53 Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region. To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies. Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children. |
Viral gastroenteritis in rotavirus negative hospitalized children <5 years of age from the independent states of the former Soviet Union
Chhabra P , Samoilovich E , Yermalovich M , Chernyshova L , Gheorghita S , Cojocaru R , Shugayev N , Sahakyan G , Lashkarashvili M , Chubinidze M , Zakhashvili K , Videbaek D , Wasley A , Vinje J . Infect Genet Evol 2014 28 283-288 PURPOSE: Rotavirus causes nearly 40% of all hospitalizations for AGE among children <5 years of age in the NIS of the former Soviet Union. The etiologic role of other established gastroenteritis viruses in this age group is unknown. METHODS: Laboratory-confirmed rotavirus negative fecal specimens (N= 495) collected between January and December 2009 from children in 6 NIS (Armenia, Azerbaijan, Belarus, Georgia, Republic of Moldova and Ukraine) were tested for norovirus, sapovirus, enteric adenovirus and astrovirus by real-time RT-PCR. Genotyping was carried out by sequencing and phylogenetic analysis. RESULTS: Norovirus, enteric adenovirus, sapovirus and astrovirus were detected in 21.8%, 4.0%, 3.2%, and 1.4% of the rotavirus negative specimens, respectively. Mixed infections were identified in 4.1% of the specimens. Phylogenetic analysis showed co-circulation of several different genotypes with GII.4 Den Haag (2006b) norovirus, GI.2 sapovirus, adenovirus type 41, and astrovirus type 1 causing majority of the infections. CONCLUSION: Norovirus, enteric adenovirus, sapovirus and astrovirus account for a significant proportion (30.5%) of AGE in hospitalized children <5. years of age in 6 NIS. |
Etiology of viral gastroenteritis infections in children <5 years of age in the United States, 2008-2009
Chhabra P , Payne DC , Szilagyi PG , Edwards KM , Staat MA , Shirley SH , Wikswo M , Nix WA , Lu X , Parashar UD , Vinje J . J Infect Dis 2013 208 (5) 790-800 ![]() BACKGROUND: Although rotavirus and norovirus cause nearly 40% of severe endemic acute gastroenteritis (AGE) in children <5 years of age in the United States (US), there are limited data on the etiologic role of other enteric viruses in this age group. METHODS: We conducted active population-based surveillance in children presenting with AGE to hospitals, emergency departments, and primary care clinics in three US counties. Stool specimens from these children and from age-matched healthy controls collected between October 2008 and September 2009 were tested for enteric adenovirus, astrovirus, sapovirus, parechovirus, bocavirus and aichivirus. Typing was carried out by sequencing and phylogenetic analysis. RESULTS: Adenovirus, astrovirus, sapovirus, parechovirus, bocavirus and aichivirus were detected in the stool specimens of 11.8%, 4.9%, 5.4%, 4.8%, 1.4% and 0.2% of AGE patients and 1.8%, 3.0%, 4.2%, 4.4%, 2.4% and 0% of healthy controls, respectively. Adenovirus [type-41], astrovirus [types-1, 2, 3, 4, 8], sapovirus [GI and GII], parechovirus [types-1, 3, 4, 5] and bocavirus [types-1, 2, 3] were found co-circulating. CONCLUSIONS: Adenovirus, astrovirus, and sapovirus infections were detected in 22.1% of the specimens from children <5 years of age who had medical visits for AGE and tested negative for rota- and norovirus. No causal role for parechovirus and bocavirus was found. |
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