Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 93 Records) |
Query Trace: Davis CT [original query] |
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Pathogenesis and transmission assessment of three swine-origin influenza A(H3N2) viruses with zoonotic risk to humans isolated in the U.S from 2017-2020
Sun X , Belser JA , Pulit-Penaloza JA , Brock N , Pappas C , Zanders N , Jang Y , Jones J , Tumpey TM , Davis CT , Maines TR . J Infect Dis 2024 229 (4) 1107-1111 The sporadic occurrence of human infections with swine-origin influenza A(H3N2) viruses and the continual emergence of novel A(H3N2) viruses in swine herds underscore the necessity for ongoing assessment of the pandemic risk posed by these viruses. Here, we selected 3 recent novel swine-origin A(H3N2) viruses isolated between 2017 to 2020, bearing hemagglutinins from the 1990.1, 2010.1, or 2010.2 clades, and evaluated their ability to cause disease and transmit in a ferret model. We conclude that despite considerable genetic variances, all 3 contemporary swine-origin A(H3N2) viruses displayed a capacity for robust replication in the ferret respiratory tract and were also capable of limited airborne transmission. These findings highlight the continued public health risk of swine-origin A(H3N2) strains, especially in human populations with low cross-reactive immunity. |
Avian influenza A(H5) virus circulation in live bird markets in Vietnam, 2017-2022
Nguyen DT , Sumner KM , Nguyen TTM , Phan MQ , Hoang TM , Vo CD , Nguyen TD , Nguyen PT , Yang G , Jang Y , Jones J , Olsen SJ , Gould PL , Nguyen LV , Davis CT . Influenza Other Respir Viruses 2023 17 (12) e13245 BACKGROUND: Highly pathogenic avian influenza A(H5) human infections are a global concern, with many A(H5) human cases detected in Vietnam, including a case in October 2022. Using avian influenza virus surveillance from March 2017-September 2022, we described the percent of pooled samples that were positive for avian influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses in live bird markets (LBMs) in Vietnam. METHODS: Monthly at each LBM, 30 poultry oropharyngeal swab specimens and five environmental samples were collected. Samples were pooled in groups of five and tested for influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses by real-time reverse-transcription polymerase chain reaction. Trends in the percent of pooled samples that were positive for avian influenza were summarized by LBM characteristics and time and compared with the number of passively detected avian influenza outbreaks using Spearman's rank correlation. RESULTS: A total of 25,774 pooled samples were collected through active surveillance at 167 LBMs in 24 provinces; 36.9% of pooled samples were positive for influenza A, 3.6% A(H5), 1.9% A(H5N1), 1.1% A(H5N6), and 0.2% A(H5N8). Influenza A(H5) viruses were identified January-December and at least once in 91.7% of sampled provinces. In 246 A(H5) outbreaks in poultry; 20.3% were influenza A(H5N1), 60.2% A(H5N6), and 19.5% A(H5N8); outbreaks did not correlate with active surveillance. CONCLUSIONS: In Vietnam, influenza A(H5) viruses were detected by active surveillance in LBMs year-round and in most provinces sampled. In addition to outbreak reporting, active surveillance for A(H5) viruses in settings with high potential for animal-to-human spillover can provide situational awareness. |
Reported global avian influenza detections among humans and animals during 2013-2022: Comprehensive review and analysis of available surveillance data
Szablewski CM , Iwamoto C , Olsen SJ , Greene CM , Duca LM , Davis CT , Coggeshall KC , Davis WW , Emukule GO , Gould PL , Fry AM , Wentworth DE , Dugan VG , Kile JC , Azziz-Baumgartner E . JMIR Public Health Surveill 2023 9 e46383 BACKGROUND: Avian influenza (AI) virus detections occurred frequently in 2022 and continue to pose a health, economic, and food security risk. The most recent global analysis of official reports of animal outbreaks and human infections with all reportable AI viruses was published almost a decade ago. Increased or renewed reports of AI viruses, especially high pathogenicity H5N8 and H5N1 in birds and H5N1, H5N8, and H5N6 in humans globally, have established the need for a comprehensive review of current global AI virus surveillance data to assess the pandemic risk of AI viruses. OBJECTIVE: This study aims to provide an analysis of global AI animal outbreak and human case surveillance information from the last decade by describing the circulating virus subtypes, regions and temporal trends in reporting, and country characteristics associated with AI virus outbreak reporting in animals; surveillance and reporting gaps for animals and humans are identified. METHODS: We analyzed AI virus infection reports among animals and humans submitted to animal and public health authorities from January 2013 to June 2022 and compared them with reports from January 2005 to December 2012. A multivariable regression analysis was used to evaluate associations between variables of interest and reported AI virus animal outbreaks. RESULTS: From 2013 to 2022, 52.2% (95/182) of World Organisation for Animal Health (WOAH) Member Countries identified 34 AI virus subtypes during 21,249 outbreaks. The most frequently reported subtypes were high pathogenicity AI H5N1 (10,079/21,249, 47.43%) and H5N8 (6722/21,249, 31.63%). A total of 10 high pathogenicity AI and 6 low pathogenicity AI virus subtypes were reported to the WOAH for the first time during 2013-2022. AI outbreaks in animals occurred in 26 more Member Countries than reported in the previous 8 years. Decreasing World Bank income classification was significantly associated with decreases in reported AI outbreaks (P<.001-.02). Between January 2013 and June 2022, 17/194 (8.8%) World Health Organization (WHO) Member States reported 2000 human AI virus infections of 10 virus subtypes. H7N9 (1568/2000, 78.40%) and H5N1 (254/2000, 12.70%) viruses accounted for the most human infections. As many as 8 of these 17 Member States did not report a human case prior to 2013. Of 1953 human cases with available information, 74.81% (n=1461) had a known animal exposure before onset of illness. The median time from illness onset to the notification posted on the WHO event information site was 15 days (IQR 9-30 days; mean 24 days). Seasonality patterns of animal outbreaks and human infections with AI viruses were very similar, occurred year-round, and peaked during November through May. CONCLUSIONS: Our analysis suggests that AI outbreaks are more frequently reported and geographically widespread than in the past. Global surveillance gaps include inconsistent reporting from all regions and human infection reporting delays. Continued monitoring for AI virus outbreaks in animals and human infections with AI viruses is crucial for pandemic preparedness. |
Mitigating Pandemic Risk with Influenza A Virus Field Surveillance at a Swine-Human Interface (preprint)
Rambo-Martin BL , Keller MW , Wilson MM , Nolting JM , Anderson TK , Vincent AL , Bagal UR , Jang Y , Neuhaus EB , Davis CT , Bowman AS , Wentworth DE , Barnes JR . bioRxiv 2019 585588 Working overnight at a large swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, nanopore-sequenced 13 IAV genomes from samples collected, and in real-time, determined that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current pre-pandemic candidate vaccine viruses (CVV). We developed and used a portable IAV sequencing and analysis platform called Mia (Mobile Influenza Analysis) to complete and characterize full-length consensus genomes approximately 18 hours after unpacking the mobile lab. Swine are important animal IAV reservoirs that have given rise to pandemic viruses via zoonotic transmission. Genomic analyses of IAV in swine are critical to understanding pandemic risk of viruses in this reservoir, and characterization of viruses circulating in exhibition swine enables rapid comparison to current seasonal influenza vaccines and CVVs. The Mia system rapidly identified three genetically distinct swine IAV lineages from three subtypes: A(H1N1), A(H3N2) and A(H1N2). Additional analysis of the HA protein sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 portion of the hemagglutinin of these viruses and the most closely related pre-2009 CVV. All virus sequences were emailed to colleagues at CDC who initiated development of a synthetically derived CVV designed to provide an optimal antigenic match with the viruses detected in the exhibition. In subsequent months, this virus caused 13 infections in humans, and was the dominant variant virus in the US detected in 2018. Had this virus caused a severe outbreak or pandemic, our proactive surveillance efforts and CVV derivation would have provided an approximate 8 week time advantage for vaccine manufacturing. This is the first report of the use of field-derived nanopore sequencing data to initiate a real-time, actionable public health countermeasure. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines (preprint)
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Hossain J , Lin X , Lester S , Pusch E , Jones J , Cui D , Chatterjee P , Jenks HM , Morantz E , Larson G , Hatta M , Harcourt J , Tamin A , Li Y , Tao Y , Zhao K , Burroughs A , Wong T , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Laufer Halpin AS , Lee JS , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan V , Wentworth DE , Zhou B , Batra D , Beck A , Caravas J , Cintron-Moret R , Cook PW , Gerhart J , Gulvik C , Hassell N , Howard D , Knipe K , Kondor RJ , Kovacs N , Lacek K , Mann BR , McMullan LK , Moser K , Paden CR , Martin BR , Schmerer M , Shepard S , Stanton R , Stark T , Sula E , Tymeckia K , Unoarumhi Y . bioRxiv 2021 30 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic. |
Antiviral susceptibility of clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses isolated from birds and mammals in the United States, 2022
Nguyen HT , Chesnokov A , De La Cruz J , Pascua PNQ , Mishin VP , Jang Y , Jones J , Di H , Ivashchenko AA , Killian ML , Torchetti MK , Lantz K , Wentworth DE , Davis CT , Ivachtchenko AV , Gubareva LV . Antiviral Res 2023 217 105679 Clade 2.3.4.4 b highly pathogenic avian influenza (HPAI) A (H5N1) viruses that are responsible for devastating outbreaks in birds and mammals pose a potential threat to public health. Here, we evaluated their susceptibility to influenza antivirals. Of 1015 sequences of HPAI A (H5N1) viruses collected in the United States during 2022, eight viruses (∼0.8%) had a molecular marker of drug resistance to an FDA-approved antiviral: three adamantane-resistant (M2-V27A), four oseltamivir-resistant (NA-H275Y), and one baloxavir-resistant (PA-I38T). Additionally, 31 viruses contained mutations that may reduce susceptibility to inhibitors of neuraminidase (NA) (n = 20) or cap-dependent endonuclease (CEN) (n = 11). A panel of 22 representative viruses was tested phenotypically. Overall, clade 2.3.4.4  b A (H5N1) viruses lacking recognized resistance mutations were susceptible to FDA-approved antivirals. Oseltamivir was least potent at inhibiting NA activity, while the investigational NA inhibitor AV5080 was most potent, including against NA mutants. A novel NA substitution T438N conferred 12-fold reduced inhibition by zanamivir, and in combination with the known marker N295S, synergistically affected susceptibility to all five NA inhibitors. In cell culture-based assays HINT and IRINA, the PA-I38T virus displayed 75- to 108-fold and 37- to 78-fold reduced susceptibility to CEN inhibitors baloxavir and investigational AV5116, respectively. Viruses with PA-I38M or PA-A37T showed 5- to 10-fold reduced susceptibilities. As HPAI A (H5N1) viruses continue to circulate and evolve, close monitoring of drug susceptibility is needed for risk assessment and to inform decisions regarding antiviral stockpiling. |
Changes in influenza and other respiratory virus activity during the COVID-19 pandemic-United States, 2020-2021.
Olsen SJ , Winn AK , Budd AP , Prill MM , Steel J , Midgley CM , Kniss K , Burns E , Rowe T , Foust A , Jasso G , Merced-Morales A , Davis CT , Jang Y , Jones J , Daly P , Gubareva L , Barnes J , Kondor R , Sessions W , Smith C , Wentworth DE , Garg S , Havers FP , Fry AM , Hall AJ , Brammer L , Silk BJ . Am J Transplant 2021 21 (10) 3481-3486 The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced the transmission of some viral respiratory pathogens.1 In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020,2 and remained low during October 2020–May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1–4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities. |
Distinct In Vitro and In Vivo Neutralization Profiles of Monoclonal Antibodies Elicited by the Receptor Binding Domain of the Ancestral SARS-CoV-2.
Kwon HJ , Zhang J , Kosikova M , Tang W , Ortega-Rodriguez U , Peng H , Meseda CA , Pedro CL , Schmeisser F , Lu J , Kang I , Zhou B , Davis CT , Wentworth DE , Chen WH , Shriver MC , Barnes RS , Pasetti MF , Weir JP , Chen B , Xie H . J Med Virol 2023 95 (3) e28673 Broadly neutralizing antibodies against SARS-CoV-2 variants are sought to curb COVID-19 infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS-CoV-2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC(50) ) ≤ 135 ng/ml against infectious SARS-CoV-2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5 and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18-hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif (RBM) in the RBD-up conformation. A third RBD-reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross-neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID-19 convalescent sera or post-vaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS-CoV-2 variants and elicited antibody responses. This article is protected by copyright. All rights reserved. |
Swine-to-Ferret Transmission of Antigenically Drifted Contemporary Swine H3N2 Influenza A Virus Is an Indicator of Zoonotic Risk to Humans.
Souza CK , Kimble JB , Anderson TK , Arendsee ZW , Hufnagel DE , Young KM , Gauger PC , Lewis NS , Davis CT , Thor S , Vincent Baker AL . Viruses 2023 15 (2) Human-to-swine transmission of influenza A (H3N2) virus occurs repeatedly and plays a critical role in swine influenza A virus (IAV) evolution and diversity. Human seasonal H3 IAVs were introduced from human-to-swine in the 1990s in the United States and classified as 1990.1 and 1990.4 lineages; the 1990.4 lineage diversified into 1990.4.A-F clades. Additional introductions occurred in the 2010s, establishing the 2010.1 and 2010.2 lineages. Human zoonotic cases with swine IAV, known as variant viruses, have occurred from the 1990.4 and 2010.1 lineages, highlighting a public health concern. If a variant virus is antigenically drifted from current human seasonal vaccine (HuVac) strains, it may be chosen as a candidate virus vaccine (CVV) for pandemic preparedness purposes. We assessed the zoonotic risk of US swine H3N2 strains by performing phylogenetic analyses of recent swine H3 strains to identify the major contemporary circulating genetic clades. Representatives were tested in hemagglutination inhibition assays with ferret post-infection antisera raised against existing CVVs or HuVac viruses. The 1990.1, 1990.4.A, and 1990.4.B.2 clade viruses displayed significant loss in cross-reactivity to CVV and HuVac antisera, and interspecies transmission potential was subsequently investigated in a pig-to-ferret transmission study. Strains from the three lineages were transmitted from pigs to ferrets via respiratory droplets, but there were differential shedding profiles. These data suggest that existing CVVs may offer limited protection against swine H3N2 infection, and that contemporary 1990.4.A viruses represent a specific concern given their widespread circulation among swine in the United States and association with multiple zoonotic cases. |
Interspecies Transmission from Pigs to Ferrets of Antigenically Distinct Swine H1 Influenza A Viruses with Reduced Reactivity to Candidate Vaccine Virus Antisera as Measures of Relative Zoonotic Risk.
Kimble JB , Souza CK , Anderson TK , Arendsee ZW , Hufnagel DE , Young KM , Lewis NS , Davis CT , Thor S , Vincent Baker AL . Viruses 2022 14 (11) During the last decade, endemic swine H1 influenza A viruses (IAV) from six different genetic clades of the hemagglutinin gene caused zoonotic infections in humans. The majority of zoonotic events with swine IAV were restricted to a single case with no subsequent transmission. However, repeated introduction of human-seasonal H1N1, continual reassortment between endemic swine IAV, and subsequent drift in the swine host resulted in highly diverse swine IAV with human-origin genes that may become a risk to the human population. To prepare for the potential of a future swine-origin IAV pandemic in humans, public health laboratories selected candidate vaccine viruses (CVV) for use as vaccine seed strains. To assess the pandemic risk of contemporary US swine H1N1 or H1N2 strains, we quantified the genetic diversity of swine H1 HA genes, and identified representative strains from each circulating clade. We then characterized the representative swine IAV against human seasonal vaccine and CVV strains using ferret antisera in hemagglutination inhibition assays (HI). HI assays revealed that 1A.3.3.2 (pdm09) and 1B.2.1 (delta-2) demonstrated strong cross reactivity to human seasonal vaccines or CVVs. However, swine IAV from three clades that represent more than 50% of the detected swine IAVs in the USA showed significant reduction in cross-reactivity compared to the closest CVV virus: 1A.1.1.3 (alpha-deletion), 1A.3.3.3-clade 3 (gamma), and 1B.2.2.1 (delta-1a). Representative viruses from these three clades were further characterized in a pig-to-ferret transmission model and shown to exhibit variable transmission efficiency. Our data prioritize specific genotypes of swine H1N1 and H1N2 to further investigate in the risk they pose to the human population. |
Influenza A(H7N9) pandemic preparedness: Assessment of the breadth of heterologous antibody responses to emerging viruses from multiple pre-pandemic vaccines and population immunity
Levine MZ , Holiday C , Bai Y , Zhong W , Liu F , Jefferson S , Gross FL , Tzeng WP , Fries L , Smith G , Boutet P , Friel D , Innis BL , Mallett CP , Davis CT , Wentworth DE , York IA , Stevens J , Katz JM , Tumpey T . Vaccines (Basel) 2022 10 (11) Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 μg hemagglutinin (HA)/dose + AS03(A); 2. inactivated vaccine with 5.75 μg HA/dose + AS03(A;) 3. inactivated vaccine with 11.5 μg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 μg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9). |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines.
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Mann BR , Hossain J , Lin X , Lester S , Pusch EA , Jones J , Cui D , Chatterjee P , Jenks MH , Morantz EK , Larson GP , Hatta M , Harcourt JL , Tamin A , Li Y , Tao Y , Zhao K , Lacek K , Burroughs A , Wang W , Wilson M , Wong T , Park SH , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Halpin AL , McMullan LK , Lee JS , Xia H , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan VG , Wentworth DE , Zhou B . Nat Commun 2022 13 (1) 4350 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic. |
Influenza A virus circulation in backyard animals in the Pacific coast of Guatemala, 2013-2014.
Müller-Theissen ML , Azziz-Baumgartner E , Ortiz L , Szablewski CM , Alvarez D , Gonzalez-Reiche AS , Jara J , Davis CT , Cordon-Rosales C . Zoonoses Public Health 2022 69 (7) 826-834 Due to their documented epidemiological relevance as hosts for influenza A viruses (IAV), humans, poultry and pigs in backyard production systems (BPS) within wetlands could be key to the emergence of novel IAV variants able to transmit between humans or animals. To better understand the circulation of IAV at the human-animal interface of BPS within wetlands, we studied IAV in backyard duck flocks and pig herds in the Pacific Coast of Guatemala. From April 2013 to October 2014, we estimated the monthly IAV per cent seropositive and viral positive flocks and herds in two resource-limited communities. We detected antibodies in sera against the IAV nucleoprotein through ELISA. We also detected IAV viral RNA in respiratory (ducks and pigs) and cloacal (ducks) swabs through rRT-PCR directed at the matrix gene. We attempted viral isolation in eggs or MDCK cells followed by sequencing from swabs positive for IAV. During our study period, IAV seropositivity in duck flocks was 38%, and viral positivity was 23% (n = 86 BPS sampled). IAV seropositivity in pig herds was 42%, and viral positivity was 20% (n = 90 BPS sampled). Both flocks and herds had detectable antibodies against IAV mostly year-round, and IAV was detected in several months. We isolated an H3N2 virus from one pig sampled at the end of 2013. Standard nucleotide BLAST searches indicate that the isolated virus was similar to seasonal viruses circulating in humans, suggesting human-to-pig transmission. Our data show concurrent circulation of IAV in multiple species of poultry and pigs that were commingled in rudimentary conditions in proximity to humans, but no significant risk factors could be identified. |
First human infection of avian influenza A(H5N6) virus reported in Lao People's Democratic Republic, February-March 2021
Sengkeopraseuth B , Co KC , Leuangvilay P , Mott JA , Khomgsamphanh B , Somoulay V , Tsuyuoka R , Chiew M , Ketmayoon P , Jones J , Pusch E , Jang Y , Barnes J , Davis CT , Phommachanh P , Khamphaphongphane B , Olsen SJ , Xangsayyarath P . Influenza Other Respir Viruses 2021 16 (2) 181-185 In March 2021, Lao People's Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5-year-old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security. |
Crossroads of highly pathogenic H5N1: overlap between wild and domestic birds in the Black Sea-Mediterranean impacts global transmission.
Hill NJ , Smith LM , Muzaffar SB , Nagel JL , Prosser DJ , Sullivan JD , Spragens KA , Demattos CA , Demattos CC , El Sayed L , Erciyas-Yavuz K , Davis CT , Jones J , Kis Z , Donis RO , Newman SA , Takekawa JY . Virus Evol 2021 7 (1) veaa093 Understanding transmission dynamics that link wild and domestic animals is a key element of predicting the emergence of infectious disease, an event that has highest likelihood of occurring wherever human livelihoods depend on agriculture and animal trade. Contact between poultry and wild birds is a key driver of the emergence of highly pathogenic avian influenza (HPAI), a process that allows for host switching and accelerated reassortment, diversification, and spread of virus between otherwise unconnected regions. This study addresses questions relevant to the spillover of HPAI at a transmission hotspot: what is the nature of the wild bird-poultry interface in Egypt and adjacent Black Sea-Mediterranean countries and how has this contributed to outbreaks occurring worldwide? Using a spatiotemporal model of infection risk informed by satellite tracking of waterfowl and viral phylogenetics, this study identified ecological conditions that contribute to spillover in this understudied region. Results indicated that multiple ducks (Northern Shoveler and Northern Pintail) hosted segments that shared ancestry with HPAI H5 from both clade 2.2.1 and clade 2.3.4 supporting the role of Anseriformes in linking viral populations in East Asia and Africa over large distances. Quantifying the overlap between wild ducks and H5N1-infected poultry revealed an increasing interface in late winter peaking in early spring when ducks expanded their range before migration, with key differences in the timing of poultry contact risk between local and long-distance migrants. Copyright © 2020 Published by Oxford University Press 2020. This work is written by a US Government employee and is in the public domain in the US. |
Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic - United States, 2020-2021.
Olsen SJ , Winn AK , Budd AP , Prill MM , Steel J , Midgley CM , Kniss K , Burns E , Rowe T , Foust A , Jasso G , Merced-Morales A , Davis CT , Jang Y , Jones J , Daly P , Gubareva L , Barnes J , Kondor R , Sessions W , Smith C , Wentworth DE , Garg S , Havers FP , Fry AM , Hall AJ , Brammer L , Silk BJ . MMWR Morb Mortal Wkly Rep 2021 70 (29) 1013-1019 The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities. |
Laboratory evaluation of two point-of-care detection systems for early and accurate detectaion of influenza in the Lao People's Democratic Republic.
Kittikraisak W , Khamphaphongphane B , Xayadeth S , Oulay VS , Khanthamaly V , Sengvilaipaseuth O , Davis CT , Yang G , Zanders N , Mott JA , Xangsayarath P . Int J Infect Dis 2020 104 214-221 BACKGROUND: We evaluated molecular-based point-of-care influenza detection systems in a laboratory prior to the field evaluations of on-site specimen testing. METHODS: Performance of 1) insulated isothermal PCR on the POCKIT(TM) device and 2) real-time reverse transcription-PCR (rRT-PCR) on a MyGo Mini device were evaluated using human clinical specimens, beta-propiolactone-inactivated influenza viruses, and RNA controls. The rRT-PCR carried out on a CXF-96(TM) Real-time Detection System was used as a gold standard for comparisons. RESULTS: Both systems demonstrated 100% sensitivity and specificity and test results were in 100% agreement with the gold standard. POCKIT(TM) only correctly identified influenza A(M gene) in clinical specimens due to the unavailability of typing and subtyping reagents for human influenza viruses, while MyGo Mini had either a one log higher or the same sensitivity in detecting influenza viruses in clinical specimens compared to the gold standard. For inactivated viruses and/or viral RNA, the analytic sensitivity of POCKIT(TM) was shown to be comparable to, or more sensitive, than the gold standard. The analytic sensitivity of MyGo Mini had mixed results depending on the types and subtypes of influenza viruses. CONCLUSIONS: The performance of the two systems in a laboratory is promising and supports further evaluation in field settings. |
Detection and Characterization of Swine-origin Influenza A(H1N1) Pandemic 2009 Viruses in Humans Following Zoonotic Transmission.
Cook PW , Stark T , Jones J , Kondor R , Zanders N , Benfer J , Scott S , Jang Y , Janas-Martindale A , Lindstrom S , Blanton L , Schiltz J , Tell R , Griesser R , Shult P , Reisdorf E , Danz T , Fry A , Barnes J , Vincent A , Wentworth DE , Davis CT . J Virol 2020 95 (2) Human-to-swine transmission of seasonal influenza viruses has led to sustained human-like influenza viruses circulating in the United States swine population. While some reverse zoonotic-origin viruses adapt and become enzootic in swine, nascent reverse zoonoses may result in virus detections that are difficult to classify as 'swine-origin' or 'human-origin' due to the genetic similarity of circulating viruses. This is the case for human-origin influenza A(H1N1) pandemic 2009 (pdm09) viruses detected in pigs following numerous reverse zoonosis events since the 2009 pandemic. We report the identification of two human infections with A(H1N1)pdm09 viruses originating from swine hosts and classify them as 'swine-origin' variant influenza viruses based on phylogenetic analysis and sequence comparison methods. Phylogenetic analyses of viral genomes from two cases revealed these viruses were reassortants containing A(H1N1)pdm09 HA and NA genes with genetic combinations derived from the triple reassortant internal gene cassette. Follow-up investigations determined that one individual had direct exposure to swine in the week preceding illness onset, while another did not report swine exposure. The swine-origin A(H1N1) variant cases were resolved by full genome sequence comparison of the variant viruses to swine influenza genomes. However, if reassortment does not result in the acquisition of swine-associated genes and swine virus genomic sequences are not available from the exposure source future cases may not be discernible. We have developed a pipeline that performs maximum likelihood analyses, a k-mer-based set difference algorithm, and random forest algorithms to identify swine-associated sequences in the hemagglutinin gene to differentiate between human-origin and swine-origin A(H1N1)pdm09 viruses.IMPORTANCE Influenza virus infects a wide range of hosts resulting in illnesses that vary from asymptomatic cases to severe pneumonia and death. Viral transfer can occur between human and non-human hosts resulting in human and non-human origin viruses circulating in novel hosts. In this work, we have identified the first case of a swine-origin influenza A(H1N1)pdm09 virus resulting in a human infection. This shows that as these viruses not only circulate in swine hosts, but are continuing to evolve and distinguish themselves from previously circulating human-origin influenza viruses. The development of techniques for distinguishing human-origin and swine-origin viruses are necessary for the continued surveillance of influenza viruses. We show that unique genetic signatures can differentiate circulating swine-associated strains from circulating human-associated strains of influenza A(H1N1)pdm09, and these signatures can be used to enhance surveillance of swine-origin influenza. |
Genetically and antigenically divergent influenza A(H9N2) viruses exhibit differential replication and transmission phenotypes in mammalian models.
Belser JA , Sun X , Brock N , Pappas C , Pulit-Penaloza JA , Zeng H , Jang Y , Jones J , Carney PJ , Chang J , Van Long N , Diep NT , Thor S , Di H , Yang G , Cook PW , Creager HM , Wang D , McFarland J , Van Dong P , Wentworth DE , Tumpey TM , Barnes JR , Stevens J , Davis CT , Maines TR . J Virol 2020 94 (17) Low pathogenicity avian influenza A(H9N2) viruses, enzootic in poultry populations in Asia, are associated with fewer confirmed human infections but higher rates of seropositivity compared to A(H5) or A(H7) subtype viruses. Co-circulation of A(H5) and A(H7) viruses leads to the generation of reassortant viruses bearing A(H9N2) internal genes with markers of mammalian adaptation, warranting continued surveillance in both avian and human populations. Here, we describe active surveillance efforts in live poultry markets in Vietnam in 2018 and compare representative viruses to G1 and Y280 lineage viruses that have infected humans. Receptor binding properties, pH thresholds for HA activation, in vitro replication in human respiratory tract cells, and in vivo mammalian pathogenicity and transmissibility were investigated. While A(H9N2) viruses from both poultry and humans exhibited features associated with mammalian adaptation, one human isolate from 2018, A/Anhui-Lujiang/39/2018, exhibited increased capacity for replication and transmission, demonstrating the pandemic potential of A(H9N2) viruses.IMPORTANCE A(H9N2) influenza viruses are widespread in poultry in many parts of the world, and for over twenty years, have sporadically jumped species barriers to cause human infection. As these viruses continue to diversify genetically and antigenically, it is critical to closely monitor viruses responsible for human infections, to ascertain if A(H9N2) viruses are acquiring properties that make them better suited to infect and spread among humans. In this study, we describe an active poultry surveillance system established in Vietnam to identify the scope of influenza viruses present in live bird markets and the threat they pose to human health. Assessment of a recent A(H9N2) virus isolated from an individual in China in 2018 is also reported and was found to exhibit properties of adaptation to humans and, importantly, show similarities to strains isolated from the live bird markets of Vietnam. |
Mammalian pathogenicity and transmissibility of low pathogenic avian influenza H7N1 and H7N3 viruses isolated from North America in 2018
Belser JA , Sun X , Brock N , Pulit-Penaloza JA , Jones J , Zanders N , Davis CT , Tumpey TM , Maines TR . Emerg Microbes Infect 2020 9 (1) 1037-1045 ABSTRACTLow pathogenic avian influenza (LPAI) H7 subtype viruses are infrequently, but persistently, associated with outbreaks in poultry in North America. These LPAI outbreaks provide opportunities for the virus to develop enhanced virulence and transmissibility in mammals and have previously resulted in both occasional acquisition of a highly pathogenic avian influenza (HPAI) phenotype in birds and sporadic cases of human infection. Two notable LPAI H7 subtype viruses caused outbreaks in 2018 in North America: LPAI H7N1 virus in chickens and turkeys, representing the first confirmed H7N1 infection in poultry farms in the United States, and LPAI H7N3 virus in turkeys, a virus subtype often associated with LPAI-to-HPAI phenotypes. Here, we investigated the replication capacity of representative viruses from these outbreaks in human respiratory tract cells and mammalian pathogenicity and transmissibility in the mouse and ferret models. We found that the LPAI H7 viruses replicated to high titre in human cells, reaching mean peak titres generally comparable to HPAI H7 viruses. Replication was efficient in both mammalian species, causing mild infection, with virus primarily limited to respiratory tract tissues. The H7 viruses demonstrated a capacity to transmit to naive ferrets in a direct contact setting. These data support the need to perform routine risk assessments of LPAI H7 subtype viruses, even in the absence of confirmed human infection. |
Development of an RNA strand-specific hybridization assay to differentiate replicating versus non-replicating influenza A virus.
Yang G , Hodges EN , Winter J , Zanders N , Shcherbik S , Bousse T , Murray JR , Muraduzzaman AKM , Rahman M , Alamgir ASM , Sabrina Flora M , Blanton L , Barnes JR , Wentworth DE , Davis CT . J Clin Microbiol 2020 58 (6) Replication of influenza A virus (IAV) from negative-sense viral RNA (vRNA) requires the generation of positive-sense RNA (+RNA). Most molecular assays, such as conventional real-time RT-PCR (rRT-PCR), detect total RNA in a sample without differentiating vRNA from +RNA. These assays are not designed to distinguish IAV infection versus exposure of an individual to an environment enriched with IAVs, but wherein no viral replication occurs. We, therefore, developed a strand-specific hybridization (SSH) assay that differentiates between vRNA and +RNA and quantifies relative levels of each RNA species. The SSH assay exhibited a linearity of 7 logs with a lower limit of detection of 6.0x10(2) copies of molecules per reaction. No signal was detected in samples with a high load of non-target template or influenza B virus, demonstrating assay specificity. IAV +RNA was detected at 2-4 hours post-inoculation of MDCK cells, whereas synthesis of cold-adapted IAV +RNA was significantly impaired at 37 degrees C. The SSH assay was then used to test IAV rRT-PCR positive nasopharyngeal specimens collected from individuals exposed to IAV at swine exhibitions (n=7) or while working at live bird markets (n=2). The SSH assay was able to differentiate vRNA and +RNA in samples collected from infected, symptomatic individuals versus individuals who were exposed to IAV in the environment, but had no active viral replication. Data generated with this technique, especially when coupled with clinical data and assessment of seroconversion, will facilitate differentiation of actual IAV infection with replicating virus versus individuals exposed to high levels of environmental contamination, but without virus infection. |
Pandemic potential of highly pathogenic avian influenza clade 2.3.4.4 A(H5) viruses
Yamaji R , Saad MD , Davis CT , Swayne DE , Wang D , Wong FYK , McCauley JW , Peiris JSM , Webby RJ , Fouchier RAM , Kawaoka Y , Zhang W . Rev Med Virol 2020 30 (3) e2099 The panzootic caused by A/goose/Guangdong/1/96-lineage highly pathogenic avian influenza (HPAI) A(H5) viruses has occurred in multiple waves since 1996. From 2013 onwards, clade 2.3.4.4 viruses of subtypes A(H5N2), A(H5N6), and A(H5N8) emerged to cause panzootic waves of unprecedented magnitude among avian species accompanied by severe losses to the poultry industry around the world. Clade 2.3.4.4 A(H5) viruses have expanded in distinct geographical and evolutionary pathways likely via long distance migratory bird dispersal onto several continents and by poultry trade among neighboring countries. Coupled with regional circulation, the viruses have evolved further by reassorting with local viruses. As of February 2019, there have been 23 cases of humans infected with clade 2.3.4.4 H5N6 viruses, 16 (70%) of which had fatal outcomes. To date, no HPAI A(H5) virus has caused sustainable human-to-human transmission. However, due to the lack of population immunity in humans and ongoing evolution of the virus, there is a continuing risk that clade 2.3.4.4 A(H5) viruses could cause an influenza pandemic if the ability to transmit efficiently among humans was gained. Therefore, multisectoral collaborations among the animal, environmental, and public health sectors are essential to conduct risk assessments and develop countermeasures to prevent disease and to control spread. In this article, we describe an assessment of the likelihood of clade 2.3.4.4 A(H5) viruses gaining human-to-human transmissibility and impact on human health should such human-to-human transmission occur. This structured analysis assessed properties of the virus, attributes of the human population, and ecology and epidemiology of these viruses in animal hosts. |
Influenza A virus field surveillance at a swine-human interface
Rambo-Martin BL , Keller MW , Wilson MM , Nolting JM , Anderson TK , Vincent AL , Bagal UR , Jang Y , Neuhaus EB , Davis CT , Bowman AS , Wentworth DE , Barnes JR . mSphere 2020 5 (1) While working overnight at a swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, Nanopore sequenced 13 IAV genomes from samples we collected, and predicted in real time that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current prepandemic candidate vaccine viruses (CVVs). We developed and used a portable IAV sequencing and analysis platform called Mia (Mobile Influenza Analysis) to complete and characterize full-length consensus genomes approximately 18 h after unpacking the mobile lab. Exhibition swine are a known source for zoonotic transmission of IAV to humans and pose a potential pandemic risk. Genomic analyses of IAV in swine are critical to understanding this risk, the types of viruses circulating in swine, and whether current vaccines developed for use in humans would be predicted to provide immune protection. Nanopore sequencing technology has enabled genome sequencing in the field at the source of viral outbreaks or at the bedside or pen-side of infected humans and animals. The acquired data, however, have not yet demonstrated real-time, actionable public health responses. The Mia system rapidly identified three genetically distinct swine IAV lineages from three subtypes, A(H1N1), A(H3N2), and A(H1N2). Analysis of the hemagglutinin (HA) sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 of these viruses and the most closely related CVV. As an exercise in pandemic preparedness, all sequences were emailed to CDC collaborators who initiated the development of a synthetically derived CVV.IMPORTANCE Swine are influenza virus reservoirs that have caused outbreaks and pandemics. Genomic characterization of these viruses enables pandemic risk assessment and vaccine comparisons, though this typically occurs after a novel swine virus jumps into humans. The greatest risk occurs where large groups of swine and humans comingle. At a large swine exhibition, we used Nanopore sequencing and on-site analytics to interpret 13 swine influenza virus genomes and identified an influenza virus cluster that was genetically highly varied to currently available vaccines. As part of the National Strategy for Pandemic Preparedness exercises, the sequences were emailed to colleagues at the CDC who initiated the development of a synthetically derived vaccine designed to match the viruses at the exhibition. Subsequently, this virus caused 14 infections in humans and was the dominant U.S. variant virus in 2018. |
Swine influenza A viruses and the tangled relationship with humans
Anderson TK , Chang J , Arendsee ZW , Venkatesh D , Souza CK , Kimble JB , Lewis NS , Davis CT , Vincent AL . Cold Spring Harb Perspect Med 2020 11 (3) Influenza A viruses (IAVs) are the causative agents of one of the most important viral respiratory diseases in pigs and humans. Human and swine IAV are prone to interspecies transmission, leading to regular incursions from human to pig and vice versa. This bidirectional transmission of IAV has heavily influenced the evolutionary history of IAV in both species. Transmission of distinct human seasonal lineages to pigs, followed by sustained within-host transmission and rapid adaptation and evolution, represent a considerable challenge for pig health and production. Consequently, although only subtypes of H1N1, H1N2, and H3N2 are endemic in swine around the world, extensive diversity can be found in the hemagglutinin (HA) and neuraminidase (NA) genes, as well as the remaining six genes. We review the complicated global epidemiology of IAV in swine and the inextricably entangled implications for public health and influenza pandemic planning. |
The first report of human infection with avian influenza A(H9N2) virus in Oman: the need for a One Health approach
Al-Mayahi Z , Al Kindi H , Davis CT , Al-Rawahi B , Al-Yaqoubi F , Jang Y , Jones J , Barnes JR , Davis W , Shu B , Lynch B , Wentworth DE , Al-Maskari Z , Al Maani A , Al Abri S . Int J Infect Dis 2019 91 169-173 After detection of the first human case of avian influenza A subtype H9N2 in 1998, more than 40 cases were diagnosed worldwide. The spread of the virus, on the other hand, is more remarkable and significant in global poultry populations causing notable economic losses despite its low pathogenicity. Many surveillance studies and activities conducted in several countries proved the predominance of this virus subtype. We present a case report of A(H9N2) virus infection in a 14-month-old female from Oman. It is the first A(H9N2) human case reported from Oman and the Gulf Cooperation Countries and the second country outside of southern and eastern Asia, cases were also detected in Egypt. The patient had bronchial asthma and presented with high-grade temperature and symptoms of lower respiratory tract infection that necessitated admission to a high dependency unit in a tertiary care hospital. It is of urgency that a multisectoral One Health approach be established to combat the threat of avian influenza at the animal-human interface. In addition to enhancements of surveillance and control in poultry, there is a need to develop screening and preventive programs for high-risk occupations. |
Susceptibility of influenza A, B, C, and D viruses to Baloxavir
Mishin VP , Patel MC , Chesnokov A , De La Cruz J , Nguyen HT , Lollis L , Hodges E , Jang Y , Barnes J , Uyeki T , Davis CT , Wentworth DE , Gubareva LV . Emerg Infect Dis 2019 25 (10) 1969-1972 Baloxavir showed broad-spectrum in vitro replication inhibition of 4 types of influenza viruses (90% effective concentration range 1.2-98.3 nmol/L); susceptibility pattern was influenza A > B > C > D. This drug also inhibited influenza A viruses of avian and swine origin, including viruses that have pandemic potential and those resistant to neuraminidase inhibitors. |
Update: Influenza Activity - United States and Worldwide, May 19-September 28, 2019, and Composition of the 2020 Southern Hemisphere Influenza Vaccine
Epperson S , Davis CT , Brammer L , Abd Elal AI , Ajayi N , Barnes J , Budd AP , Burns E , Daly P , Dugan VG , Fry AM , Jang Y , Johnson SJ , Kniss K , Kondor R , Grohskopf LA , Gubareva L , Merced-Morales A , Sessions W , Stevens J , Wentworth DE , Xu X , Jernigan D . MMWR Morb Mortal Wkly Rep 2019 68 (40) 880-884 During May 19-September 28, 2019,* low levels of influenza activity were reported in the United States, with cocirculation of influenza A and influenza B viruses. In the Southern Hemisphere seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries. In late September, the World Health Organization (WHO) recommended components for the 2020 Southern Hemisphere influenza vaccine and included an update to the A(H3N2) and B/Victoria-lineage components. Annual influenza vaccination is the best means for preventing influenza illness and its complications, and vaccination before influenza activity increases is optimal. Health care providers should recommend vaccination for all persons aged >/=6 months who do not have contraindications to vaccination (1). |
Detection of highly pathogenic avian influenza A(H5N6) viruses in waterfowl in Bangladesh.
Yang G , Chowdury S , Hodges E , Rahman MZ , Jang Y , Hossain ME , Jones J , Stark TJ , Di H , Cook PW , Ghosh S , Azziz-Baumgartner E , Barnes JR , Wentworth DE , Kennedy E , Davis CT . Virology 2019 534 36-44 Bangladesh has reported repeated outbreaks of highly pathogenic avian influenza (HPAI) A(H5) viruses in poultry since 2007. Because of the large number of live poultry markets (LPM) relative to the population density of poultry throughout the country, these markets can serve as sentinel sites for HPAI A(H5) detection. Through active LPM surveillance during June 2016-June 2017, HPAI A(H5N6) viruses along with 14 other subtypes of influenza A viruses were detected. The HPAI A(H5N6) viruses belonged to clade 2.3.4.4 and were likely introduced into Bangladesh around March 2016. Human infections with influenza clade 2.3.4.4 viruses in Bangladesh have not been identified, but the viruses had several molecular markers associated with potential human infection. Vigilant surveillance at the animal-human interface is essential to identify emerging avian influenza viruses with the potential to threaten public and animal health. |
Detection of oseltamivir-resistant zoonotic and animal influenza A viruses using the rapid influenza antiviral resistance test.
Hodges EN , Mishin VP , De la Cruz J , Guo Z , Nguyen HT , Fallows E , Stevens J , Wentworth DE , Davis CT , Gubareva LV . Influenza Other Respir Viruses 2019 13 (5) 522-7 Mutations in the influenza virus neuraminidase (NA) that cause reduced susceptibility to the NA inhibitor (NAI) oseltamivir may occur naturally or following antiviral treatment. Currently, detection uses either a traditional NA inhibition assay or gene sequencing to identify known markers associated with reduced inhibition by oseltamivir. Both methods are laborious and require trained personnel. The influenza antiviral resistance test (iART), a prototype system developed by Becton, Dickinson and Company for research use only, offers a rapid and simple method to identify such viruses. This study investigated application of iART to influenza A viruses isolated from non-human hosts with a variety of NA subtypes (N1-N9). |
Comparison of nucleic acid extraction methods for next-generation sequencing of avian influenza A virus from ferret respiratory samples.
Di H , Thor S , Trujillo AA , Stark T , Marinova-Petkova A , Jones J , Wentworth DE , Barnes J , Davis CT . J Virol Methods 2019 270 95-105 Influenza A virus is a negative-sense RNA virus with a segmented genome consisting of eight RNA segments. Avian influenza A virus (AIV) primarily infects avian hosts and sporadically infects mammals, which can lead to adaptation to new species. Next-generation sequencing (NGS) of emerging AIV genomes extracted from respiratory samples collected on sequential days from animal models and clinical patients enables analysis of the emergence of evolutionary variants within the virus population over time. However, obtaining codon complete AIV genome at a sufficient coverage depth for nucleotide variant calling remains a challenge, especially from post-inoculation respiratory samples collected at late time points that have low viral titers. In this study, nasal wash samples from ferrets inoculated with different subtypes of AIV were collected on various days post-inoculation. Each nasal wash sample was aliquoted and extracted using five commercially available nucleic acid extraction methods. Extracted influenza virus RNA was amplified and NGS conducted using Illumina Mi-Seq. For each nasal wash sample, completeness of AIV genome segments and coverage depth were compared among five extraction methods. Nucleic acids extracted by MagNA pure compact RNA isolation consistently yielded codon complete sequences for all eight genome segments at the required coverage depth at each time point sampled. The study revealed that DNase treatment was critical to the amplification of influenza genome segments and the downstream success of codon complete NGS from nasal wash samples. The findings from this study can be applied to improve NGS of influenza and other RNA viruses that infect the respiratory tract and are collected from respiratory samples. |
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