ResearchPad - influenza https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[When two are better than one: Modeling the mechanisms of antibody mixtures]]> https://www.researchpad.co/article/elastic_article_14641 With the rise of new antibody combinations in therapeutic regimens, it is important to understand how antibodies work together as well as individually. Here, we investigate the specific case of monoclonal antibodies targeting a cancer-causing receptor or the influenza virus and develop a statistical mechanical framework that predicts the effectiveness of a mixture of antibodies. The power of this model lies in its ability to make a large number of predictions based on a limited amount of data. For example, once 10 antibodies have been individually characterized and their epitopes have been mapped, our model can predict how any of the 210 = 1024 combinations will behave. This predictive power can aid therapeutic efforts by assessing which combinations of antibodies will elicit the most effective response.

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<![CDATA[Low response in eliciting neuraminidase inhibition activity of sera among recipients of a split, monovalent pandemic influenza vaccine during the 2009 pandemic]]> https://www.researchpad.co/article/elastic_article_14470 Antibodies against influenza virus neuraminidase (NA) protein prevent releasing of the virus from host cells and spreading of infection foci and are considered the ‘second line of defence’ against influenza. Haemagglutinin inhibition antibody-low responders (HI-LRs) are present among influenza split vaccine recipients. The NA inhibition (NAI) antibody response in vaccinees is worth exploring, especially those in the HI-LRs population. We collected pre- and post-vaccination sera from 61 recipients of an inactivated, monovalent, split vaccine against A/H1N1pdm09 and acute and convalescent sera from 49 unvaccinated patients naturally infected with the A/H1N1pdm09 virus during the 2009 influenza pandemic. All samples were subjected to haemagglutinin inhibition (HI), NAI and neutralisation assays. Most paired sera from naturally infected patients exhibited marked elevation in the NAI activity, and seroconversion rates (SCR) among HI-LRs and HI-responders (HI-Rs) were 60% and 87%, respectively; however, those from vaccinees displayed low increase in the NAI activity, and the SCR among HI-LRs and HI-Rs were 0% and 12%, respectively. In both HI-LRs and HI-Rs, vaccination with the inactivated, monovalent, split vaccine failed to elicit the NAI activity efficiently in the sera of the naive population, compared with the natural infection. Hence, the improvement of influenza vaccines is warranted to elicit not only HI but also NAI antibodies.

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<![CDATA[Virus detections among patients with severe acute respiratory illness, Northern Vietnam]]> https://www.researchpad.co/article/elastic_article_13805 Severe acute respiratory illness (SARI) is a major cause of death and morbidity in low- and middle-income countries, however, the etiologic agents are often undetermined due to the lack of molecular diagnostics in hospitals and clinics. To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017–2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. Patient demographics were recorded and used to epidemiologically describe the infections. Among military and civilian cases of SARI, 184 (52.9%) tested positive for one or more respiratory viruses. Influenza A virus was the most prevalent virus detected (64.7%), followed by influenza B virus (29.3%), enterovirus (3.8%), adenovirus (1.1%), and coronavirus (1.1%). Risk factor analyses demonstrated an increased risk of influenza A virus detection among military hospital patients (adjusted OR, 2.0; 95% CI, 1.2–3.2), and an increased risk of influenza B virus detection among patients enrolled in year 2017 (adjusted OR, 7.9; 95% CI, 2.7–22.9). As influenza A and B viruses were commonly associated with SARI and are treatable, SARI patients entering these hospitals would benefit if the hospitals were able to adapt onsite molecular diagnostics.

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<![CDATA[Not sick enough to worry? "Influenza-like" symptoms and work-related behavior among healthcare workers and other professionals: Results of a global survey]]> https://www.researchpad.co/article/elastic_article_13852 Healthcare workers (HCWs) and non-HCWs may contribute to the transmission of influenza-like illness (ILI) to colleagues and susceptible patients by working while sick (presenteeism). The present study aimed to explore the views and behavior of HCWs and non-HCWs towards the phenomenon of working while experiencing ILI.MethodsThe study was a cross-sectional online survey conducted between October 2018 and January 2019 to explore sickness presenteeism and the behaviour of HCWs and non-HCWs when experiencing ILI. The survey questionnaire was distributed to the members and international networks of the International Society of Antimicrobial Chemotherapy (ISAC) Infection Prevention and Control (IPC) Working Group, as well as via social media platforms, including LinkedIn, Twitter and IPC Blog.ResultsIn total, 533 respondents from 49 countries participated (Europe 69.2%, Asia-Pacific 19.1%, the Americas 10.9%, and Africa 0.8%) representing 249 HCWs (46.7%) and 284 non-HCWs (53.2%). Overall, 312 (58.5%; 95% confidence interval [CI], 56.2–64.6) would continue to work when sick with ILI, with no variation between the two categories. Sixty-seven (26.9%) HCWs and forty-six (16.2%) non-HCWs would work with fever alone (p<0 .01) Most HCWs (89.2–99.2%) and non-HCWs (80%-96.5%) would work with “minor” ILI symptoms, such as sore throat, sinus cold, fatigue, sneezing, runny nose, mild cough and reduced appetite.ConclusionA future strategy to successfully prevent the transmission of ILI in healthcare settings should address sick-leave policy management, in addition to encouraging the uptake of influenza vaccine. ]]> <![CDATA[Recent Progress in Anti-Influenza Chemotherapy]]> https://www.researchpad.co/article/N291f3eed-ea2a-4fa6-a595-d92832f24bd9

Influenza virus infections in high risk individuals, such as infants, the elderly, and patients with cardiopulmonary disorders or immunocompromised states, cause severe manifestations which often result in fatalities. The emergence of a new antigen type of influenza A virus (H5N1) in Hong Kong during 1997 and 1998 threatened a possible pandemic of a new influenza infection.

The investigation for anti-influenza chemotherapies has progressed in the last decade whereas clinical trials of new compounds have been limited to amantadine, rimantadine and ribavirin. Fusion inhibitors which directly inhibit conformational change of haemagglutinin (HA), protease inhibitors which inhibit cleavage of HA to HA1 and HA2, RNA transcription inhibitors which inhibit cap formation of mRNA and antisense oligonucleotides targeted at mRNA of PB2 (a part of viral RNA polymerase) have been reported, in their development phases.

Recently, 2 neuraminidase (NA) inhibitors, zanamivir and oseltamivir (GS 4104), were used in clinical trials for the treatment of patients with influenza. Both agents showed promising results. A polyoxometalate, PM-523, inhibits fusion between the virus envelope and cell membrane and inhibits the penetration of the virus into cells. This compound has shown potent anti-influenza activity and synergistic inhibitory activity in combination with ribavirin or zanamivir in vitro and in vivo.

Resistant strains for zanamivir, oseltamivir or PM-523 have been isolated. The analysis of mutation points of these strains have contributed to the investigation of the antiviral mechanisms of action of these compounds and the mechanism of resistance of the mutants to these compounds.

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<![CDATA[Effects of Air Pollution and Other Environmental Exposures on Estimates of Severe Influenza Illness, Washington, USA]]> https://www.researchpad.co/article/N9c6ec5a1-e195-484f-aae7-aa4aa0f641b2

Ecologic models of influenza burden may be confounded by other exposures that share winter seasonality. We evaluated the effects of air pollution and other environmental exposures in ecologic models estimating influenza-associated hospitalizations. We linked hospitalization data, viral surveillance, and environmental data, including temperature, relative humidity, dew point, and fine particulate matter for 3 counties in Washington, USA, for 2001–2012. We used negative binomial regression models to estimate the incidence of influenza-associated respiratory and circulatory (RC) hospitalizations and to assess the effect of adjusting for environmental exposures on RC hospitalization estimates. The modeled overall incidence rate of influenza-associated RC hospitalizations was 31/100,000 person-years. The environmental parameters were statistically associated with RC hospitalizations but did not appreciably affect the event rate estimates. Modeled influenza-associated RC hospitalization rates were similar to published estimates, and inclusion of environmental covariates in the model did not have a clinically important effect on severe influenza estimates.

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<![CDATA[Effectiveness of Live Poultry Market Interventions on Human Infection with Avian Influenza A(H7N9) Virus, China ]]> https://www.researchpad.co/article/N117bb014-c2b9-42ea-b03e-d0eedee29880

Various interventions for live poultry markets (LPMs) have emerged to control outbreaks of avian influenza A(H7N9) virus in mainland China since March 2013. We assessed the effectiveness of various LPM interventions in reducing transmission of H7N9 virus across 5 annual waves during 2013–2018, especially in the final wave. With the exception of waves 1 and 4, various LPM interventions reduced daily incidence rates significantly across waves. Four LPM interventions led to a mean reduction of 34%–98% in the daily number of infections in wave 5. Of these, permanent closure provided the most effective reduction in human infection with H7N9 virus, followed by long-period, short-period, and recursive closures in wave 5. The effectiveness of various LPM interventions changed with the type of intervention across epidemics. Permanent LPM closure should be considered to maintain sufficient effectiveness of interventions and prevent the recurrence of H7N9 epidemics.

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<![CDATA[Human Adenovirus 7d Strains Associated with Influenza-Like Illness, New York, USA, 2017–2019]]> https://www.researchpad.co/article/N6f1bb054-d72c-4177-b994-c73ed2ab718f

Human adenovirus 7d is a respiratory pathogen capable of causing acute respiratory disease of variable severity. Phylogenetic analysis of whole-genome sequences of 15 strains isolated from cases of influenza-like-illness during 2017–2019 demonstrated the circulation of 2 distinct clades of genomic variant 7d in colleges in New York, USA.

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<![CDATA[Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings—International Travel-Related Measures]]> https://www.researchpad.co/article/Ncae74e08-5dde-4a90-914b-9e21318d7056

International travel–related nonpharmaceutical interventions (NPIs), which can include traveler screening, travel restrictions, and border closures, often are included in national influenza pandemic preparedness plans. We performed systematic reviews to identify evidence for their effectiveness. We found 15 studies in total. Some studies reported that NPIs could delay the introduction of influenza virus. However, no available evidence indicated that screening of inbound travelers would have a substantial effect on preventing spread of pandemic influenza, and no studies examining exit screening were found. Some studies reported that travel restrictions could delay the start of local transmission and slow international spread, and 1 study indicated that small Pacific islands were able to prevent importation of pandemic influenza during 1918–19 through complete border closure. This limited evidence base indicates that international travel-related NPIs would have limited effectiveness in controlling pandemic influenza and that these measures require considerable resources to implement.

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<![CDATA[Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings—Personal Protective and Environmental Measures]]> https://www.researchpad.co/article/N69a2c7f7-bb8e-4949-b84c-c99ef7e99363

There were 3 influenza pandemics in the 20th century, and there has been 1 so far in the 21st century. Local, national, and international health authorities regularly update their plans for mitigating the next influenza pandemic in light of the latest available evidence on the effectiveness of various control measures in reducing transmission. Here, we review the evidence base on the effectiveness of nonpharmaceutical personal protective measures and environmental hygiene measures in nonhealthcare settings and discuss their potential inclusion in pandemic plans. Although mechanistic studies support the potential effect of hand hygiene or face masks, evidence from 14 randomized controlled trials of these measures did not support a substantial effect on transmission of laboratory-confirmed influenza. We similarly found limited evidence on the effectiveness of improved hygiene and environmental cleaning. We identified several major knowledge gaps requiring further research, most fundamentally an improved characterization of the modes of person-to-person transmission.

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<![CDATA[Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings—Social Distancing Measures]]> https://www.researchpad.co/article/N556814b1-8960-43b7-a409-a68b4fcce62f

Influenza virus infections are believed to spread mostly by close contact in the community. Social distancing measures are essential components of the public health response to influenza pandemics. The objective of these mitigation measures is to reduce transmission, thereby delaying the epidemic peak, reducing the size of the epidemic peak, and spreading cases over a longer time to relieve pressure on the healthcare system. We conducted systematic reviews of the evidence base for effectiveness of multiple mitigation measures: isolating ill persons, contact tracing, quarantining exposed persons, school closures, workplace measures/closures, and avoiding crowding. Evidence supporting the effectiveness of these measures was obtained largely from observational studies and simulation studies. Voluntary isolation at home might be a more feasible social distancing measure, and pandemic plans should consider how to facilitate this measure. More drastic social distancing measures might be reserved for severe pandemics.

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<![CDATA[Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission]]> https://www.researchpad.co/article/Nca8f7add-a1d9-4373-9c77-344aec55ea94

Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season and a vaccine for a novel pandemic virus manufactured using current technology will not be available fast enough to mitigate the effect of the first pandemic wave. Antivirals can be effective against many different influenza viruses but have not thus far been used extensively for outbreak control. Baloxavir, a recently licensed antiviral drug that targets the influenza virus endonuclease, has been shown to reduce virus shedding more effectively than oseltamivir, a widely used neuraminidase inhibitor drug. Thus it is possible that treatment with baloxavir might also interrupt onward virus transmission. To test this, we utilized the ferret model, which is the most commonly used animal model to study influenza virus transmission. We established a subcutaneous baloxavir administration method in ferrets which achieved similar pharmacokinetics to the approved human oral dose. Transmission studies were then conducted in two different locations with different experimental setups to compare the onward transmission of A(H1N1)pdm09 virus from infected ferrets treated with baloxavir, oseltamivir or placebo to naïve sentinel ferrets exposed either indirectly in adjacent cages or directly by co-housing. We found that baloxavir treatment reduced infectious viral shedding in the upper respiratory tract of ferrets compared to placebo, and reduced the frequency of transmission amongst sentinels in both experimental setups, even when treatment was delayed until 2 days post-infection. In contrast, oseltamivir treatment did not substantially affect viral shedding or transmission compared to placebo. We did not detect the emergence of baloxavir-resistant variants in treated animals or in untreated sentinels. Our results support the concept that antivirals which decrease viral shedding could also reduce influenza transmission in the community.

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<![CDATA[Knowledge of Infectious Disease Specialists Regarding Aspergillosis Complicating Influenza, United States]]> https://www.researchpad.co/article/Nd4d7653d-1a24-44c8-ab0c-a94fa74e43db

In an online survey, we found that nearly one fifth of physicians in the United States who responded had seen or heard about a case of invasive pulmonary aspergillosis after severe influenza at their institution. However, <10% routinely used galactomannan testing to test for this fungus in patients with severe influenza.

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<![CDATA[Illness Severity in Hospitalized Influenza Patients by Virus Type and Subtype, Spain, 2010–2017]]> https://www.researchpad.co/article/N08cfe80f-2251-4cd4-9494-1bc659e5f812

Influenza A(H1N1)pdm09 caused more hospitalizations, intensive care unit admissions, and deaths than influenza A(H3N2) or B.

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<![CDATA[Antigenic Variant of Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2019]]> https://www.researchpad.co/article/N8ad266a5-d0d7-4dab-a29d-c6e5cb41c806

In China, influenza A(H7N9) virus appeared in 2013, then mutated into a highly pathogenic virus, causing outbreaks among poultry and cases in humans. Since September 2017, extensive use of the corresponding vaccine, H7-Re1, successfully reduced virus prevalence. However, in 2019, a novel antigenic variant emerged, posing considerable economic and public health threats.

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<![CDATA[Interspecies Transmission of Reassortant Swine Influenza A Virus Containing Genes from Swine Influenza A(H1N1)pdm09 and A(H1N2) Viruses]]> https://www.researchpad.co/article/N8149724d-779a-4259-8c9d-f5004f42b93e

Influenza A(H1N1)pdm09 (pH1N1) virus has become established in swine in the United Kingdom and currently co-circulates with previously enzootic swine influenza A virus (IAV) strains, including avian-like H1N1 and human-like H1N2 viruses. During 2010, a swine influenza A reassortant virus, H1N2r, which caused mild clinical disease in pigs in the United Kingdom, was isolated. This reassortant virus has a novel gene constellation, incorporating the internal gene cassette of pH1N1-origin viruses and hemagglutinin and neuraminidase genes of swine IAV H1N2 origin. We investigated the pathogenesis and infection dynamics of the H1N2r isolate in pigs (the natural host) and in ferrets, which represent a human model of infection. Clinical and virologic parameters were mild in both species and both intraspecies and interspecies transmission was observed when initiated from either infected pigs or infected ferrets. This novel reassortant virus has zoonotic and reverse zoonotic potential, but no apparent increased virulence or transmissibility, in comparison to pH1N1 viruses.

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<![CDATA[Seasonal characteristics of influenza vary regionally across US]]> https://www.researchpad.co/article/5c897716d5eed0c4847d2428

Given substantial regional differences in absolute humidity across the US and our understanding of the relationship between absolute humidity and influenza, we may expect important differences in regional seasonal influenza activity. Here, we assessed cross-seasonal influenza activity by comparing counts of positive influenza A and B rapid test results during the influenza season versus summer baseline periods for the 2016/2017 and 2017/2018 influenza years. Our analysis indicates significant regional patterns in cross-seasonal influenza activity, with relatively fewer influenza cases during the influenza season compared to summertime baseline periods in humid areas of the US, particularly in Florida and Hawaii. The cross-seasonal ratios vary from year-to-year and influenza type, but the geographic patterning of the ratios is relatively consistent. Mixed-effects regression models indicated absolute humidity during the influenza season was the strongest predictor of cross-seasonal influenza activity, suggesting a relationship between absolute humidity and cross-seasonal influenza activity. There was also evidence that absolute humidity during the summer plays a role, as well. This analysis suggests that spatial variation in seasonal absolute humidity levels may generate important regional differences in seasonal influenza activity and dynamics in the US.

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<![CDATA[Comparison of the new fully automated extraction platform eMAG to the MagNA PURE 96 and the well-established easyMAG for detection of common human respiratory viruses]]> https://www.researchpad.co/article/5c75ac8ad5eed0c484d089f7

Respiratory viral infections constitute the majority of samples tested in the clinical virology laboratory during the winter season, and are mainly diagnosed using molecular assays, namely real-time PCR (qPCR). Therefore, a high-quality extraction process is critical for successful, reliable and sensitive qPCR results. Here we aimed to evaluate the performance of the newly launched eMAG compared to the fully automated MagNA PURE 96 (Roche, Germany) and to the semi-automated easyMAG (bioMerieux, France) extraction platforms. For this analysis, we assessed and compared the analytic and clinical performance of the three platforms, using 262 archived respiratory samples positive or negative to common viruses regularly examined in our laboratory (influenza A, B, H1N1pdm, Respiratory Syncytial Virus (RSV), human Metapneumovirus (hMPV), parainfluenza-3, adenovirus and negative samples). In addition, quantitated virus controls were used to determine the limit of detection of each extraction method.

In all categories tested, eMAG results were comparable to those of the easyMAG and MagNa PURE 96, highly sensitive for all viruses and over 98% clinical specificity and sensitivity for all viruses tested. Together with its high level of automation, the bioMerieux eMAG is a high-quality extraction platform enabling effective molecular analysis and is mostly suitable for medium-sized laboratories.

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<![CDATA[Potent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor-binding head domains]]> https://www.researchpad.co/article/5c61e8e4d5eed0c48496f33e

Seasonal influenza virus infections can cause significant morbidity and mortality, but the threat from the emergence of a new pandemic influenza strain might have potentially even more devastating consequences. As such, there is intense interest in isolating and characterizing potent neutralizing antibodies that target the hemagglutinin (HA) viral surface glycoprotein. Here, we use cryo-electron microscopy (cryoEM) to decipher the mechanism of action of a potent HA head-directed monoclonal antibody (mAb) bound to an influenza H7 HA. The epitope of the antibody is not solvent accessible in the compact, prefusion conformation that typifies all HA structures to date. Instead, the antibody binds between HA head protomers to an epitope that must be partly or transiently exposed in the prefusion conformation. The “breathing” of the HA protomers is implied by the exposure of this epitope, which is consistent with metastability of class I fusion proteins. This structure likely therefore represents an early structural intermediate in the viral fusion process. Understanding the extent of transient exposure of conserved neutralizing epitopes also may lead to new opportunities to combat influenza that have not been appreciated previously.

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<![CDATA[Even a good influenza forecasting model can benefit from internet-based nowcasts, but those benefits are limited]]> https://www.researchpad.co/article/5c5df345d5eed0c484581069

The ability to produce timely and accurate flu forecasts in the United States can significantly impact public health. Augmenting forecasts with internet data has shown promise for improving forecast accuracy and timeliness in controlled settings, but results in practice are less convincing, as models augmented with internet data have not consistently outperformed models without internet data. In this paper, we perform a controlled experiment, taking into account data backfill, to improve clarity on the benefits and limitations of augmenting an already good flu forecasting model with internet-based nowcasts. Our results show that a good flu forecasting model can benefit from the augmentation of internet-based nowcasts in practice for all considered public health-relevant forecasting targets. The degree of forecast improvement due to nowcasting, however, is uneven across forecasting targets, with short-term forecasting targets seeing the largest improvements and seasonal targets such as the peak timing and intensity seeing relatively marginal improvements. The uneven forecasting improvements across targets hold even when “perfect” nowcasts are used. These findings suggest that further improvements to flu forecasting, particularly seasonal targets, will need to derive from other, non-nowcasting approaches.

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