James W. Rudge, Nui Inthalaphone, Rebecca Pavlicek, Phimpha Paboriboune, Bruno Flaissier, Chou Monidarin, Nicolas Steenkeste, Viengmon Davong, Manivanh Vongsouvath, K. A. Bonath, Melinda Messaoudi, Mitra Saadatian-Elahi, Paul Newton, Hubert Endtz, David Dance, Glaucia Paranhos Baccala, Valentina Sanchez Picot

by James W. Rudge, Nui Inthalaphone, Rebecca Pavlicek, Phimpha Paboriboune, Bruno Flaissier, Chou Monidarin, Nicolas Steenkeste, Viengmon Davong, Manivanh Vongsouvath, K. A. Bonath, Melinda Messaoudi, Mitra Saadatian-Elahi, Paul Newton, Hubert Endtz, David Dance, Glaucia Paranhos Baccala, Valentina Sanchez Picot Respiratory diseases are a major contributor to morbidity and mortality in many tropical countries, including Lao PDR. However, little has been published regarding viral or bacterial pathogens that can contribute to influenza-like illness (ILI) in a community setting. We report on the results of a community-based surveillance that prospectively monitored the incidence of ILI and its causative pathogens in Vientiane capital in Lao PDR. A cohort of 995 households, including 4885 study participants, were followed-up between May 2015 and May 2016. Nasopharyngeal swabs, throat swabs, and sputum specimens were collected from ILI cases identified through active case-finding. Real-Time PCR was used to test nasopharyngeal swabs for 21 respiratory pathogens, while throat and sputum samples were subjected to bacterial culture. Generalized linear mixed models were used to assess potential risk factors for associations with ILI. In total, 548 episodes of ILI were reported among 476 (9.7%) of the study participants and 330 (33.2%) of the study households. The adjusted estimated incidence of ILI within the study area was 10.7 (95%CI: 9.4–11.9) episodes per 100 person-years. ILI was significantly associated with age group (p

Julien Coussement, David Lebeaux, Najla El Bizri, Vincent Claes, Michel Kohnen, Deborah Steensels, Isabelle Étienne, Hélène Salord, Emmanuelle Bergeron, Veronica Rodriguez-Nava

by Julien Coussement, David Lebeaux, Najla El Bizri, Vincent Claes, Michel Kohnen, Deborah Steensels, Isabelle Étienne, Hélène Salord, Emmanuelle Bergeron, Veronica Rodriguez-Nava Background Transplant recipients are at risk of pulmonary nocardiosis, a life-threatening opportunistic infection caused by Nocardia species. Given the limitations of conventional diagnostic techniques (i.e., microscopy and culture), a polymerase chain reaction (PCR)-based assay was developed to detect Nocardia spp. on clinical samples. While this test is increasingly being used by transplant physicians, its performance characteristics are not well documented. We evaluated the performance characteristics of this test on bronchoalveolar lavage (BAL) fluid samples from lung transplant recipients (LTRs). Methods We prospectively included all BAL samples from LTRs undergoing bronchoscopy at our institution between December 2016 and June 2017 (either surveillance or clinically-indicated bronchoscopies). Presence of microbial pathogens was assessed using techniques available locally (including microscopy and 10-day culture for Nocardia). BAL samples were also sent to the French Nocardiosis Observatory (Lyon, France) for the Nocardia PCR-based assay. Transplant physicians and patients were blinded to the Nocardia PCR results. Results We included 29 BAL samples from 21 patients (18 surveillance and 11 clinically-indicated bronchoscopies). Nocardiosis was not diagnosed in any of these patients by conventional techniques. However, Nocardia PCR was positive in five BAL samples from five of the patients (24%, 95% confidence interval: 11–45%); four were asymptomatic and undergoing surveillance bronchoscopy, and one was symptomatic and was later diagnosed with influenza virus infection. None of the five PCR-positive patients died or were diagnosed with nocardiosis during the median follow-up of 21 months after the index bronchoscopy (range: 20–23 months). Conclusions In this prospective study, Nocardia PCR was positive on BAL fluid from one fourth of the LTRs. Nocardia PCR-based assays should be used with caution on respiratory samples from LTRs because of the possible detection of airway colonization using this technique. Larger studies are required to determine the usefulness of the Nocardia PCR-based assay in transplant recipients.…

Karawita, Anjana C.; Tong, Marcus Z.W.; Short, Kirsty R.

Purpose of review A delicate balance exists between a protective and detrimental immune response to an invading viral pathogen. Here, we review the latest advancements in our understanding of immunity and immunopathology during H7N9 influenza A virus (IAV) infections and its relevance to disease management and diagnosis. Recent findings Recent studies have highlighted the role of specific leukocytes in the pathogenesis of H7N9 IAV infections and potential diagnostic role that host cytokine profiles can play in forecasting disease severity. Furthermore, alterations in diet have emerged as a possible preventive measure for severe IAV infections. Summary The recent emergence and continued evolution of H7N9 IAVs have emphasized the threat that these avian viruses pose to human health. Understanding the role of the host immune response in both disease protection and pathogenesis is an essential first step in the creation of novel therapeutic and preventive measures for H7N9 IAV infections. Correspondence to Kirsty R. Short, Brisbane, Qld Australia. Tel: +61 7 3365 3732; e-mail: k.short@uq.edu.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Han A, Czajkowski L, Donaldson A, et al.

AbstractBackgroundThe development of vaccines and therapeutics have relied on healthy volunteer influenza challenge studies. A validated human infection model with wild-type A(H1N1)pdm09 was reported previously.ObjectiveTo characterize a wild-type Influenza A/Bethesda/MM1/H3N2 challenge virus in healthy volunteers.MethodsParticipants received a single dose of a cell-based, reverse-genetics, GMP-produced wild-type influenza A/H3N2/2011 virus intranasally and were isolated at the NIH Clinical Center for > 9 days. Dose escalation was performed from 104 to 107 TCID50. Viral shedding and clinical disease were evaluated daily.ResultsOf 37 participants challenged, 16 (43%) had viral shedding and 27 (73%) developed symptoms with 12 participants (32%) experiencing mild to moderate influenza disease (MMID) defined as shedding and symptoms. Only participants receiving the 106 and 107 TCID50 doses experienced MMID at 44% and 40%, respectively. Symptom severity peaked on day 3 while most viral shedding occurred 1-2 days after challenge. Only 10 (29%) participants had > fourfold rise in hemagglutinin inhibition (HAI) antibody titer after challenge.ConclusionsThe A/Bethesda/MM1/H3N2 challenge virus safely induced MMID in healthy volunteers, but caused less MMID than the A(H1N1)pdm09 challenge virus even at the highest dose. There was less detection of shedding though the incidence of symptoms was similar to A(H1N1)pdm09. Fewer serum anti-HA antibody responses with less MMID indicate that preexisting immunity factors other than anti-HA antibody may limit shedding in healthy volunteers. This A/Bethesda/MM1/H3N2 challenge virus can be utilized in future studies to further explore pathogenesis and immunity and to evaluate vaccine candidates.

Abstract Background Detecting the onset of influenza epidemic is important for epidemiological surveillance and for investigating the factors driving spatiotemporal transmission patterns. Most approaches define the epidemic onset based on thresholds, which use subjective criteria and are specific to individual surveillance systems. Methods We applied the empirical threshold method (ETM), together with two non-thresholding methods, including the maximum curvature method (MCM) that we proposed and the segmented regression method (SRM), to determine onsets of influenza epidemics in each prefecture of Japan, using sentinel surveillance data of influenza-like illness (ILI) from 2012/2013 through 2017/2018. Performance of the MCM and SRM was evaluated, in terms of epidemic onset, end, and duration, with those derived from the ETM using the nationwide epidemic onset indicator of 1.0 ILI case per sentinel per week. Results The MCM and SRM yielded complete estimates for each of Japan’s 47 prefectures. In contrast, ETM estimates for Kagoshima during 2012/2013 and for Okinawa during all six influenza seasons, except 2013/2014, were invalid. The MCM showed better agreement in all estimates with the ETM than the SRM (R2 = 0.82, p 

Najat Bdeir, Prerna Arora, Sabine Gärtner, Markus Hoffmann, Udo Reichl, Stefan Pöhlmann, Michael Winkler

by Najat Bdeir, Prerna Arora, Sabine Gärtner, Markus Hoffmann, Udo Reichl, Stefan Pöhlmann, Michael Winkler Influenza A virus (IAV) infection poses a serious health threat and novel antiviral strategies are needed. Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus. The antiviral activity of DIPs is exerted by a DI genomic RNA segment that usually contains a large deletion and suppresses amplification of wt segments, potentially by competing for cellular and viral resources. DI-244 is a naturally occurring prototypic segment 1-derived DI RNA in which most of the PB2 open reading frame has been deleted and which is currently developed for antiviral therapy. At present, coinfection with wt virus is required for production of DI-244 particles which raises concerns regarding biosafety and may complicate interpretation of research results. Here, we show that cocultures of 293T and MDCK cell lines stably expressing codon optimized PB2 allow production of DI-244 particles solely from plasmids and in the absence of helper virus. Moreover, we demonstrate that infectivity of these particles can be quantified using MDCK-PB2 cells. Finally, we report that the DI-244 particles produced in this novel system exert potent antiviral activity against H1N1 and H3N2 IAV but not against the unrelated vesicular stomatitis virus. This is the first report of DIP production in the absence of infectious IAV and may spur efforts to develop DIPs for antiviral therapy.

Phillips, Z. N., Brizuela, C., Jennison, A. V., Staples, M., Grimwood, K., Seib, K. L., Jennings, M. P., Atack, J. M.

Non-typeable Haemophilus influenzae (NTHi) is a major human pathogen, responsible for several acute and chronic infections of the respiratory tract. The incidence of invasive infections caused by NTHi is increasing world-wide. NTHi is able to colonise the nasopharynx asymptomatically, and the exact change(s) responsible for transition from benign carriage to overt disease are not understood. We have previously reported that phase-variation (the rapid and reversible ON-OFF switching of gene expression) of particular lipooligosaccharide (LOS) glycosyltransferases occurs during transition from colonising the nasopharynx to invading the middle ear. Variation in the structure of the LOS is dependent on the ON/OFF expression status of each of the glycosyltransferases responsible for LOS biosynthesis. In this study we surveyed a collection of invasive NTHi isolates for ON/OFF expression status of seven phase-variable LOS glycosyltransferases. We report that the expression state of the LOS biosynthetic genes oafA ON and lic2A OFF show a correlation with invasive NTHi isolates. We hypothesise that these gene expression changes contribute to the invasive potential of NTHi. OafA expression, which is responsible for the addition of an O-acetyl group onto the LOS, has been shown to impart a phenotype of increased serum resistance, and may serve as a marker for invasive NTHi.…

Hadara L. Norowitz, Timothy Morello, Hadassah M. Kupfer, Stephan A. Kohlhoff, Tamar A. Smith-Norowitz

by Hadara L. Norowitz, Timothy Morello, Hadassah M. Kupfer, Stephan A. Kohlhoff, Tamar A. Smith-Norowitz This study aims to assess prospectively whether there is an association between frequencies of upper respiratory tract infections (URTI) or asthma in early childhood and failed otoacoustic emission (OAE) screenings later in life. There are no clear recommendations for hearing testing following acute otitis media (AOM) infection. This is a retrospective, practice based chart review. Participants from a primary care setting were 517 pre-adolescent and adolescent children (49.9% female) (ages 10–21; mean, 15 y/o), who had presented with at least one specific bacterial URTI (AOM, Group A Streptococcus (GAS) tonsillitis, or Influenza) during childhood. Hearing testing was recorded incidentally at all subsequent routine health care maintenance visits (OAE hearing screen). Simple linear regression analyses were performed using R (v3.4.4). We found that number of episodes of AOM infections strongly correlated with number of failed OAE screenings later in life (F = 76.37; P =…

Skowronski D, De Serres G, Orenstein W.

Abstract Background We assessed the utility of a multi-target, real-time PCR assay for Bordetella pertussis detection and diagnosis in patients with severe respiratory illness (SRI), influenza-like illness (ILI), and asymptomatic controls. Methods Real-time PCR detection of IS481, pIS1001, hIS1001 and ptxS1 was performed on nasopharyngeal specimens (SRI, ILI and controls) and induced sputum (SRI) collected from June 2012 to May 2016 through respiratory illness surveillance. Using PCR cycle threshold (Ct) value cut-offs, IS481 positive cases were classified as confirmed (Ct 

Abstract Background To improve national influenza vaccination recommendations, additional data on influenza A and B virus circulation are needed. Here, we describe the circulation of influenza A and B in the Czech Republic during 16 seasons. Methods This was a retrospective analysis of data collected from the 2000–2001 to 2015–2016 influenza seasons by the Czech Republic national influenza surveillance network. Influenza was confirmed and viral isolates subtyped by virological assays followed by antigen detection or by reverse transcriptase-polymerase chain reaction. Results Of 16,940 samples collected, 5144 (30.4%) were influenza-positive. Influenza A represented 78.6% of positive cases overall and accounted for more than 55.0% of all influenza cases in every season, except for 2005–2006 (6.0%). Both A/H1N1 and A/H3N2 were detected in most seasons, except for 2001–2002 and 2003–2004 (only A/H3N2), and 2007–2008 and 2009–2010 (only A/H1N1). Influenza B represented 21.4% of positive cases overall (range, 0.0–94.0% per season). Both influenza B lineages were detected in three seasons, a single B lineage in 11, and no B strain in two. For the 11 seasons where influenza B accounted for ≥20% of positive cases, the dominant lineage was Yamagata in six and Victoria in four. In the remaining season, the two lineages co-circulated. For two seasons (2005–2006 and 2007–2008), the B lineage in the trivalent influenza vaccine did not match the dominant circulating B lineage. Conclusions In the Czech Republic, during the 2000–2001 to 2015–2016 influenza seasons, influenza virus circulation varied considerably. Although influenza A accounted for the most cases in almost all seasons, influenza B made a substantial, sometimes dominant, contribution to influenza disease.…

Abstract Background Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. Methods Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. Results Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). Conclusion A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level.…

Musa Hindiyeh, Orna Mor, Rakefet Pando, Batya Mannasse, Areej Kabat, Hadar Assraf-Zarfati, Ella Mendelson, Danit Sofer, Michal Mandelboim

by Musa Hindiyeh, Orna Mor, Rakefet Pando, Batya Mannasse, Areej Kabat, Hadar Assraf-Zarfati, Ella Mendelson, Danit Sofer, Michal Mandelboim 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.

Marta Sisteré-Oró, Júlia Vergara-Alert, Thomas Stratmann, Sergi López-Serrano, Sonia Pina-Pedrero, Lorena Córdoba, Mónica Pérez-Maillo, Patrícia Pleguezuelos, Enric Vidal, Veljko Veljkovic, Joaquim Segalés, Jens Nielsen, Anders Fomsgaard, Ayub Darji

by Marta Sisteré-Oró, Júlia Vergara-Alert, Thomas Stratmann, Sergi López-Serrano, Sonia Pina-Pedrero, Lorena Córdoba, Mónica Pérez-Maillo, Patrícia Pleguezuelos, Enric Vidal, Veljko Veljkovic, Joaquim Segalés, Jens Nielsen, Anders Fomsgaard, Ayub Darji Swine influenza viruses (SIVs), the causal agents of swine influenza, are not only important to control due to the economic losses in the swine industry, but also can be pandemic pathogens. Vaccination is one of the most relevant strategies to control and prevent influenza infection. Current human vaccines against influenza induce strain-specific immunity and annual update is required due to the virus antigenic shift phenomena. Previously, our group has reported the use of conserved hemagglutinin peptides (HA-peptides) derived from H1-influenza virus as a potential multivalent vaccine candidate. Immunization of swine with these HA-peptides elicited antibodies that recognized and neutralized heterologous influenza viruses in vitro and demonstrated strong hemagglutination-inhibiting activity. In the present work, we cloned one HA-peptide (named NG34) into a plasmid fused with cytotoxic T lymphocyte-associated antigen (CTLA4) which is a molecule that modifies T cell activation and with an adjuvant activity interfering with the adaptive immune response. The resulting plasmid, named pCMV-CTLA4-Ig-NG34, was administered twice to animals employing a needle-free delivery approach. Two studies were carried out to test the efficacy of pCMV-CTLA4-Ig-NG34 as a potential swine influenza vaccine, one in seronegative and another in seropositive pigs against SIV. The second one was aimed to evaluate whether pCMV-CTLA4-Ig-NG34 vaccination would overcome maternally derived antibodies (MDA). After immunization, all animals were intranasally challenged with an H3N2 influenza strain. A complete elimination or significant reduction in the viral shedding was observed within the first week after the challenge in the vaccinated animals from both studies. In addition, no challenged heterologous virus load was detected in the airways of vaccinated pigs. Overall, it is suggested that the pCMV-CTLA4-Ig-NG34 vaccine formulation could potentially be used as a multivalent vaccine against influenza viruses.

L. Busson, M. Bartiaux, S. Brahim, D. Konopnicki, N. Dauby, M. Gérard, P. De Backer, K. Van Vaerenbergh, B. Mahadeb, L. Mekkaoui, M. De Foor, M. Wautier, O. Vandenberg, P. Mols, J. Levy, M. Hallin

Following publication…

Following publication of the original article [1], the author reported an error in the title:…

Mini Singh, Jenny-Ann Toribio, Angela Bullanday Scott, Peter Groves, Belinda Barnes, Kathryn Glass, Barbara Moloney, Amanda Black, Marta Hernandez-Jover

by Mini Singh, Jenny-Ann Toribio, Angela Bullanday Scott, Peter Groves, Belinda Barnes, Kathryn Glass, Barbara Moloney, Amanda Black, Marta Hernandez-Jover…

The PLOS ONE Staff

by The PLOS ONE Staff …

Dugas A, Hsieh Y, Lovecchio F, et al.

AbstractStudy objectiveAccurate diagnosis of influenza is essential for appropriate antiviral treatment in accordance with Centers for Disease Control and Prevention (CDC) guidelines. However, no clear guidance exists on whom should be tested. We sought to develop a clinical decision guideline (CDG) to inform influenza testing decisions for adult emergency department (ED) patients deemed appropriate for antiviral treatment by CDC guidelines.MethodsProspective cohort study was performed at four U.S. EDs. From November 2013 to April 2014 we enrolled adult ED patients with fever or respiratory symptoms, who met criteria for antiviral treatment per 2013 CDC guidelines. All patients were tested for influenza using PCR. Data were randomly split into derivation (80%) and validation (20%) datasets. A discrete set of independent variables was selected by logistic regression using the derivation set to create a scoring system, with a target sensitivity of at least 90%. The derived CDG was then validated.ResultsOf 1941 enrolled participants, 183 (9.4%) had influenza. The derived CDG included new or increased cough (2 points), headache (1 point), subjective fever (1 point), and triage temperature >100.4°C (1 point), with a score of ≥3 indicating influenza testing was warranted. The CDG had a sensitivity and specificity of 94.1% and 36.6% in the derivation set, and 91.5% and 34.6% in the validation set, respectively.ConclusionA CDG with high sensitivity was derived and validated. Incorporation into practice could standardize testing for high-risk patients in adult EDs during influenza seasons, potentially improving diagnosis and treatment.Clinical Trial RegistrationNCT01947049…

Xie C, Lau E, Yoshida T, et al.

AbstractBackgroundRespiratory virus-laden particles are commonly detected in the exhaled breath of symptomatic patients or in air sampled from healthcare settings. However, the temporal relationship of detecting virus-laden particles at non-healthcare locations versus surveillance data obtained by conventional means has not been fully assessed.MethodsFrom October 2016 to June 2018, air was sampled weekly from a university campus in Hong Kong. Viral genomes were detected and quantified by real-time RT-PCR. Logistic regression models were fitted to examine the adjusted odds ratios (aORs) of ecological and environmental factors associated with the detection of virus-laden airborne particles.ResultsInfluenza A (16.9%, 117/694) and B (4.6%, 31/694) viruses were detected at higher frequencies in air than rhinovirus (2.2%, 6/270), respiratory syncytial virus (0.4%, 1/270), or human coronaviruses (0%, 0/270). Multivariate analyses showed that increased crowdedness (aOR = 2.3, 95% confidence interval, 1.5 – 3.8, P < 0.001) and higher indoor temperature (1.2, 1.1 – 1.3, P < 0.001) were associated with detection of influenza airborne particles, but absolute humidity was not (0.9, 0.7 – 1.1, P = 0.213). Higher copies of influenza viral genome were detected from airborne particles > 4 μm in spring and < 1 μm in autumn. Influenza A(H3N2) and influenza B viruses that caused epidemics during the study period were detected in air prior to observing increased influenza activities in the community.ConclusionsAir sampling as a surveillance tool for monitoring influenza activity at public locations may provide early detection signals on influenza viruses that circulate in the community.

Danielle Vuichard-Gysin, Dominik Mertz, Eleanor Pullenayegum, Pardeep Singh, Marek Smieja, Mark Loeb

by Danielle Vuichard-Gysin, Dominik Mertz, Eleanor Pullenayegum, Pardeep Singh, Marek Smieja, Mark Loeb Predictive models have been developed for influenza but have seldom been validated. Typically they have focused on patients meeting a definition of infection that includes fever. Less is known about how models perform when more symptoms are considered. We, therefore, aimed to create and internally validate predictive scores of acute respiratory infection (ARI) symptoms to diagnose influenza virus infection as confirmed by polymerase chain reaction (PCR) from respiratory specimens. Data from a completed trial to study the indirect effect of influenza immunization in Hutterite communities were randomly split into two independent groups for model derivation and validation. We applied different multivariable modelling techniques and constructed Receiver Operating Characteristics (ROC) curves to determine predictive indexes at different cut-points. From 2008–2011, 3288 first seasonal ARI episodes and 321 (9.8%) influenza positive events occurred in 2202 individuals. In children up to 17 years, the significant predictors of influenza virus infection were fever, chills, and cough along with being of age 6 years and older. In adults, presence of chills and cough but not fever were highly specific for influenza virus infection (sensitivity 30%, specificity 96%). Performance of the models in the validation set was not significantly different. The predictors were consistently found to be significant irrespective of the multivariable technique. Symptomatic predictors of influenza virus infection vary between children and adults. The scores could assist clinicians in their test and treat decisions but the results need to be externally validated prior to application in clinical practice.

Soilemetzidou E, De Bruin E, Franz M, et al.

AbstractBackgroundInfluenza A viruses (IAVs) represent repeatedly emerging pathogens with near worldwide distribution and an unclear nonavian-host spectrum. While the natural hosts for IAV are among waterfowl species, certain mammals can be productively infected. Southern Africa is home to diverse avian and mammalian fauna for which almost no information exists on IAV dynamics.MethodsWe evaluated 111 serum samples from 14 mammalian species from Namibia for the presence of IAV-specific antibodies and tested whether host phylogeny, sociality, or diet influence viral prevalence and diversity.ResultsFree-ranging African mammals are exposed to diverse IAV subtypes. Herbivores developed antibodies against 3 different hemagglutinin (HA) subtypes, at low prevalence, while carnivores showed a higher prevalence and diversity of HA-specific antibody responses against 11 different subtypes. Host phylogeny and sociality were not significantly associated with HA antibody prevalence or subtype diversity. Both seroprevalence and HA diversity were significantly increased in carnivores regularly feeding on birds.ConclusionsThe risk of infection and transmission may be driven by diet and ecological factors that increase contact with migratory and resident waterfowl. Consequently, wild mammals, particularly those that specialize on hunting and scavenging birds, could play an important but overlooked role in influenza epizootics.

Li Wei Ang, Lin Cui, Tze Minn Mak, Yixiang Ng, Yee Sin Leo, Vernon Jian Ming Lee, Raymond Tzer‐Pin Lin

Abstract Surveillance and reporting of epidemiological features of seasonal influenza mostly are aggregates across all‐ages. We investigated age‐specific differences in distribution of influenza virus (sub)types in tropical Singapore, using laboratory‐confirmed virological data collected under the national influenza surveillance programme in 2011‐2017. The proportion of influenza‐positive specimens from outpatients with influenza‐like illness was used as an indicator of influenza activity in the community. The highest influenza positivity for age groups of 5–14 years and 15–64 years coincided in the same month in five out of the seven years under study. Influenza positivity was lowest in young children…

Lytras T, Mouratidou E, Andreopoulou A, et al.

AbstractBackgroundThe available evidence on whether neuraminidase inhibitors reduce mortality in patients with influenza is inconclusive, and focuses solely on influenza A/H1N1pdm09. We assessed whether early oseltamivir treatment (≤48 hours from symptom onset) decreases mortality compared to late treatment in a large cohort of critically ill patients with influenza of all types.MethodsThe study included all adults with laboratory-confirmed influenza hospitalized in intensive care units (ICU) in Greece over eight seasons (2010–2011 to 2017–2018) and treated with oseltamivir. The association of early oseltamivir with mortality was assessed with log-binomial models, and a competing risks analysis estimating cause-specific and subdistribution hazards for death and discharge. Effect estimates were stratified by influenza type and adjusted for multiple covariates.Results1330 patients were studied, of whom 622 (46.8%) died in the ICU. Among patients with influenza A/H3N2, early treatment was associated with significantly lower mortality (Relative Risk 0.69, 95% CrI 0.49–0.94; subdistribution Hazard Ratio 0.58, 95% CrI 0.37–0.88). This effect was purely due to an increased cause-specific hazard for discharge, while the cause-specific hazard for death was not increased. Among survivors, the median length of ICU stay was shorter with early treatment by 1.8 days (95% CrI 0.5–3.5). No effect on mortality was observed for A/H1N1 and influenza B patients. ConclusionsSeverely ill patients with suspected influenza should be promptly treated with oseltamivir, particularly when A/H3N2 is circulating. The efficacy of oseltamivir should not be assumed to be equal against all types of influenza.

Gamiño-Arroyo A, Guerrero M, McCarthy S, et al.

AbstractBackgroundEffective therapeutics for respiratory viruses are needed. Early data suggest Nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness.MethodsFrom March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥ 1 year old hospitalized with influenza-like illness at six hospitals in Mexico. Participants were randomized 1:1 to NTZ (≥12 years old, 600 mg twice daily; 4-11 and 1-3 years old, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary end point was time from first dose to hospital discharge. Influenza RT-PCR and Respifinder 22 multiplex test were used for virus detection. ClinicalTrials.gov, number NCT02057757.ResultsOf 260 participants enrolled, 257 were randomized and took at least one dose of study treatment (ITT population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization (interquartiles 25 th, 75 th) in the NTZ group was 6.5 (4.0, 9.0) days versus 7.0 (4.0, 9.0) days in the placebo group (P=0.56). Duration of hospitalization between the two treatments was similar in children (P=0.29) and adults (P=0.62), influenza A and B (P=0.32) and other respiratory viruses. 7(5.4%) and 6(4.7%) participants in the NTZ and placebo groups reported severe adverse events, respectively.ConclusionsTreatment with nitazoxanide did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from nitazoxanide.

Abstract Background Influenza surveillance is necessary for detection of emerging variants of epidemiologic and clinical significance. This study describes the epidemiology of influenza types A and B, and molecular characteristics of surface glycoproteins (hemagglutinin [HA] and neuraminidase [NA]) of influenza A subtypes: pH1N1 and H3N2 circulated in Arabian Gulf, Levant and North Africa regions during 2009–2017. Methods Analysis of phylogenetics and evolution of HA and NA genes was done using full HA and NA sequences (n = 1229) downloaded from Influenza Research Database (IRD). Results In total, 130,354 influenza positive cases were reported to WHO during study period. Of these, 50.8% were pH1N1 positive, 15.9% were H3N2 positives and 17.2% were influenza B positive. With few exceptions, all three regions were showing the typical seasonal influenza peak similar to that reported in Northern hemisphere (December–March). However, influenza activity started earlier (October) in both Gulf and North Africa while commenced later during November in Levant countries. The molecular analysis of the HA genes (influenza A subtypes) revealed similar mutations to those reported worldwide. Generally, amino acid substitutions were most frequently found in head domain in H1N1 pandemic viruses, while localized mainly in the stem region in H3N2 viruses. Expectedly, seasons with high pH1N1 influenza activity was associated with a relatively higher number of substitutions in the head domain of the HA in pH1N1 subtype. Furthermore, nucleotide variations were lower at the antigenic sites of pH1N1 viruses compared to H3N2 viruses, which experienced higher variability at the antigenic sites, reflecting the increased immunological pressure because of longer circulation and continuous vaccine changes. Analysis of NA gene of pH1N1 viruses revealed sporadic detections of oseltamivir-resistance mutation, H275Y, in 4% of reported sequences, however, none of NAI resistance mutations were found in the NA of H3N2 viruses. Conclusions Molecular characterization of H1N1 and H3N2 viruses over 9 years revealed significant differences with regard to position and function of characterized substitutions. While pH1N1 virus substitutions were mainly found in HA head domain, H3N2 virus substitutions were mostly found in HA stem domain. Additionally, more fixed substitutions were encountered in H3N2 virus compared to larger number of non-fixed substitutions in pH1N1.…

Abstract Background Despite World Health Organization recommendations, in many countries young children are not targeted for influenza vaccination. To help inform influenza vaccination policy, we examined the occurrence and burden of influenza in healthy children aged 6 to 35 months using data from a recent phase III placebo-controlled influenza vaccine trial conducted in countries in the Northern and Southern Hemispheres. Methods This was an analysis of data from participants included in the placebo arm of a phase III clinical trial in healthy children aged 6 to 35 months (EudraCT no. 2013–001231-51). Included children had never been vaccinated for influenza and were observed for one influenza season. Outcome measures included the occurrence of influenza-like illness (ILI), laboratory-confirmed influenza, virus types/subtypes, severe symptoms and complications of confirmed influenza, and healthcare use associated with confirmed influenza. Results Data from 2210 participants were analysed. ILI was reported for 811 participants (36.7%). Of these, 255 participants (31.4%) had 263 virologically confirmed episodes of influenza. The overall influenza attack rate was 11.5%. The most common influenza virus detected was A(H3N2) (40.7%), followed by B/Yamagata (23.6%), A(H1N1) (18.6%), and B/Victoria (8.0%). Grade 3 fever was reported in 24.3% of confirmed episodes, acute lower respiratory infection in 8.7%, acute otitis media in 6.1%, and pneumonia in 1.9%. In most influenza episodes (93.2%), antipyretics, analgesics, or non-steroidal anti-inflammatory drugs were taken. Antibiotics were prescribed for 41.4% of influenza episodes. More than half of the influenza episodes (57.0%) resulted in outpatient visits. Influenza resulted in overnight hospitalisation in 1.1% of episodes. Conclusions Influenza is associated with a significant burden of disease in healthy children. This analysis also revealed that antibiotics continue to be frequently used for young children with influenza. Trial registration EudraCT no. 2013–001231-51.…

Buchwald A, Tamboura B, Tennant S, et al.

AbstractIntroductionFew studies describe the Respiratory Syncytial Virus (RSV) burden in African populations, and most have utilized hospital-based surveillance. In Mali, no community-based studies exist of the incidence or epidemiology of RSV infection. This study provides the first estimates of RSV incidence in Mali. MethodsIn a cohort of infants enrolled in a clinical trial of maternal influenza vaccination, we estimate incidence of RSV-associated febrile illness in the first six months of life, and identify risk factors for RSV infection and progression to severe disease. Infants (N = 1,871) were followed from birth to six months of age and visited weekly to detect pneumonia and influenza-like illness. Baseline covariates were explored as risk factors for RSV-febrile illness and RSV-pneumonia or hospitalization. ResultsIncidence of RSV-illness was estimated at 536.8 per 1,000 person-years, and 86% (131/153) of RSV-illness episodes were positive for RSV B. RSV-illness was most frequent in the fifth month of life and associated with having older mothers, and lower parity. The incidence of RSV-associated hospitalizations was 45.6 per 1,000 person-years. Among infants with RSV-illness, males were more likely to be hospitalized. The incidence of RSV-pneumonia was 29 cases per 1,000 person-years.DiscussionIn the first six months of life, Malian infants have a high incidence of RSV illness, primarily caused by RSV B. Prevention of early RSV will require passive protection via maternal immunization in pregnancy. Mali is the first country where RSV B had been identified as the dominant subtype, with potential implications for vaccine development.

An error appeared in the initial publication of this article [Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis https://doi.org/10.1093/cid/ciy866]. This article was originally published with the two following errors:…

S. J. Olsen et al.

Jens Nielsen, Lasse S. Vestergaard, Lukas Richter, Daniela Schmid, Natalia Bustos, Tommi Asikainen, Ramona Trebbien, Gleb Denissov, Kaire Innos, Mikko J. Virtanen, Anne Fouillet, Theodore Lytras, Kassiani Gkolfinopoulou, Matthias an der Heiden, Linus Grabenhenrich, Helmut Uphoff, Anna Paldy, Janos Bobvos, Lisa Domegan, Joan O’Donnell, Matteo Scortichini, Annamaria de Martino, Joël Mossong, Kathleen England, Jackie Melillo, Liselotte van Asten, Marit MA de Lange, Ragnhild Tønnessen, Richard A. White, Susana

Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe.

Francis Sena Nuvey, Elijah Paa Edu-Quansah, George Khumalo Kuma, John Eleeza, Ernest Kenu, Samuel Sackey, Donne Ameme, Mahamat Fayiz Abakar, Katharina Kreppel, Richard Bongo Ngandolo, Edwin Afari, Bassirou Bonfoh

by Francis Sena Nuvey, Elijah Paa Edu-Quansah, George Khumalo Kuma, John Eleeza, Ernest Kenu, Samuel Sackey, Donne Ameme, Mahamat Fayiz Abakar, Katharina Kreppel, Richard Bongo Ngandolo, Edwin Afari, Bassirou Bonfoh Background Influenza-like Illness (ILI) is a medical diagnosis of possible influenza or another respiratory illness with a common set of symptoms. The deaths of four schoolchildren, during a pandemic influenza outbreak in December 2017 in Ghana, raised doubts about the ILI surveillance system’s performance. We evaluated the ILI surveillance system in the Greater Accra region, Ghana, to assess the system’s attributes and its performance on set objectives. Methods CDC guidelines were used to evaluate the data of the ILI surveillance system between 2013 and 2017. We interviewed the surveillance personnel on the system’s description and operation. Additionally, routinely entered ILI data from the National Influenza Center provided by the six sentinel sites in Accra was extracted. We sampled and reviewed 120 ILI case-investigation forms from these sites. Surveillance activities were examined on system’s performance indicators, each being scored on a scale of 1 to 3 (poorest to best performance). Results All population and age groups were under ILI surveillance over the period evaluated. Overall, 2948 suspected case-patients, including 392 (13.3%) children under-five were reported, with 219 being positive for influenza virus (Predictive value positive = 7.4%). The predominant influenza subtype was H3N2, recorded in 90 (41.1%) of positive case-patients. The system only met two out of its four objectives. None of the six sentinel sites consistently met their annual 260 suspected case-detection quota. Samples reached the laboratory on average 48 hours after collection and results were disseminated within 7 days. Of 120 case-investigation forms sampled, 91 (76.3%) were completely filled in. Conclusions The ILI surveillance system in the Greater Accra region is only partially meeting its objectives. While it is found to be sensitive, representative and timely, the data quality was sub-optimal. We recommend the determination of thresholds for alert and outbreak detection and ensuring that sentinel sites meet their weekly case-detection targets.…

Suma Vupputuri, Kevin B. Rubenstein, Alphonse J. Derus, Bernadette C. Loftus, Michael A. Horberg

by Suma Vupputuri, Kevin B. Rubenstein, Alphonse J. Derus, Bernadette C. Loftus, Michael A. Horberg Background Racial/ethnic disparities in rates of influenza vaccinations in the US remain an issue even among those with access, no out-of-pocket costs, and after adjusting for confounders. We used an approach called the Oaxaca-Blinder (OB) decomposition method to ascertain the contribution of covariates individually and in aggregate to the racial disparity in influenza vaccination. Methods We included members > = 18 years of age as of 05/01/2014 with continuous enrollment through 04/30/2015. Influenza vaccination was defined by diagnosis, procedure, or medication codes, or documentation in the immunization table. Characteristics were reported by race. Logistic regression models estimated the odds of vaccination associated with: (1) race; and (2) covariates stratified by race. The Oaxaca-Blinder (OB) method calculated the contribution of covariates to the difference or disparity in vaccination between Blacks and Whites. Results We found that among adults, 44% were vaccinated; 55% were Black; and 45% were White. Black members have 42% lower odds of vaccination than White members. The contribution of the differences in the average value of the study covariates between Black and White members (the OB covariate effect) accounted for 29% of the racial disparity. The contributions to the total White-Black disparity in vaccination included: age (16%), neighborhood median income (11%), and registration on the online patient portal (13%). The contribution of the differences in how the covariates impact vaccination (OB coefficient effect) accounted for 71% of the disparity in vaccination between Blacks and Whites. Conclusion In conclusion, equalizing average covariate values in Blacks and Whites could reduce the racial disparity in influenza vaccination by 29%. For health system vaccine campaigns, improving registration on the patient portal may be a target component of an effective system-level strategy to reduce racial disparities in vaccination. Additional information on patient-centered factors could further improve the value of the OB approach.…

Thornton A, Parry-Ford F, Tessier E, et al.

AbstractThe human risk following exposure to the European reassortant avian influenza A (H5N6) is unknown. We used routine data collected as part of public health follow-up to assess outcomes of individuals exposed to H5N6 infected wild birds in England. There were 19 separate incidents of confirmed H5N6 among wild birds in the first quarter of 2018 in England and 69 individuals exposed to infected birds during these incidents. Five exposed individuals developed respiratory symptoms. However, no H5N6 infection was detected among those individuals with respiratory symptoms who underwent diagnostic testing, indicating that the human risk from this strain remains low.

Uwe Nicolay, Esther Heijnen, Pantaleo Nacci, Peter A Patriarca, Brett Leav

Abstract Background Self-protective behaviors of social distancing and vaccination uptake vary by demographics and affect the transmission dynamics of influenza in the United States. By incorporating the socio-behavioral differences in social distancing and vaccination uptake into mathematical models of influenza transmission dynamics, we can improve our estimates of epidemic outcomes. In this study we analyze the impact of demographic disparities in social distancing and vaccination on influenza epidemics in urban and rural regions of the United States. Methods We conducted a survey of a nationally representative sample of US adults to collect data on their self-protective behaviors, including social distancing and vaccination to protect themselves from influenza infection. We incorporated this data in an agent-based model to simulate the transmission dynamics of influenza in the urban region of Miami Dade county in Florida and the rural region of Montgomery county in Virginia. Results We compare epidemic scenarios wherein the social distancing and vaccination behaviors are uniform versus non-uniform across different demographic subpopulations. We infer that a uniform compliance of social distancing and vaccination uptake among different demographic subpopulations underestimates the severity of the epidemic in comparison to differentiated compliance among different demographic subpopulations. This result holds for both urban and rural regions. Conclusions By taking into account the behavioral differences in social distancing and vaccination uptake among different demographic subpopulations in analysis of influenza epidemics, we provide improved estimates of epidemic outcomes that can assist in improved public health interventions for prevention and control of influenza.…

Janette Rahamat‐Langendoen, Hans Groenewoud, Judith Kuijpers, Willem J.G. Melchers, Gert Jan Wilt

Abstract Background At hospital admission, patients suspected of infection with influenza or respiratory syncytial virus (RSV) are placed in isolation, pending the outcome of diagnostics. In a significant number, isolated care proves unnecessary. We investigated the potential impact of molecular point‐of‐care (POC) diagnostics on patient management and in‐hospital costs. Method Prospective collection of data on resource utilization within the hospital from consecutive patients18 years or older presenting at our university medical center with symptoms of respiratory tract infection from December 2016 to April 2017. A cost analysis was conducted using Markov modeling comparing the actual course of events (based on routine diagnostic tests) with two hypothetical scenarios: when POC would impact time to diagnosis only (scenario 1) or on discharge from hospital, too (scenario 2). Results 283 Patients were included, of whom 217 (76,7%) were admitted. Influenza and RSV were detected in 31% and 7% of the patients, respectively. 54% of patients tested negative, of which 79% were kept in isolated care waiting for test results, with median duration of 24 hours. Median length of stay was 6.0 days. Mean total in‐hospital costs per patient were € 5,243. Introducing POC would lower mean costs per patient to € 4,904 (scenario 1) and € 4,206 (scenario 2). At hospital level, this would result in a total cost reduction of € 95,937 to € 293,471 in a single influenza season. Conclusions Introducing POC testing for patients presenting with symptoms of viral respiratory tract infection can reduce time‐to‐diagnosis, hospital stay and, thereby, in‐hospital costs. This article is protected by copyright. All rights reserved.

Jae‐Hyun Jeon, Minje Han, Ho‐Eun Chang, Sung‐Soo Park, Jae‐Woong Lee, Young‐Joon Ahn, Duck‐Jin Hong

Abstract Background The data on the seasonality of respiratory viruses helps to ensure the optimal vaccination period and to monitor the possible outbreaks of variant type. Objectives This study was designed to describe the molecular epidemiology and seasonality of acute respiratory infection (ARI)‐related respiratory viruses in the United Arab Emirates (UAE). Methods Both upper and lower respiratory specimens were collected for the analysis from all the patients who visited the Sheikh Khalifa Specialty Hospital (SKSH) with ARI for over 2 years. The multiplex real‐time reverse transcription polymerase chain reaction (rRT‐PCR) test was used to detect respiratory viruses, which include human adenovirus, influenza virus (FLU) A and B, respiratory syncytial virus, parainfluenza viruses, human rhinovirus (HRV), human metapneumovirus, human enterovirus, human coronavirus, and human bocavirus. Results A total of 1,362 respiratory samples were collected from 733 (53.8%) male and 629 (46.2%) female patients with ARI who visited the SKSH between November 2015 and February 2018. The rRT‐PCR test revealed an overall positivity rate of 37.2% (507/1362). The positive rate increased during winter; it was highest in December and lowest in September. FLU was the most frequently detected virus (273/1362 [20.0%]), followed by human rhinovirus (146/1362 [10.7%]). The FLU positivity rate showed two peaks, which occurred in August and December. The peak‐to‐low ratio for FLU was 2.26 (95% confidence interval: 1.52‐3.35). Conclusions The pattern of FLU in the UAE parallels to that of temperate countries. The trend of the small peak of FLU in the summer suggests a possibility of semi‐seasonal pattern in the UAE.

Fu Y, Dürrwald R, Meng F, et al.

AbstractWe analyzed the virulence of pandemic H1N1 2009 influenza A viruses in vivo and in vitro. Selected viruses isolated in 2009, 2010, 2014, and 2015 were assessed using an aerosol-mediated high-dose infection model for pigs as well as air-liquid interface cultures of differentiated airway epithelial cells. Using a dyspnea score, rectal temperature, lung lesions, and viral load in the lung as parameters, the strains from 2014–2015 were significantly less virulent than the strains isolated in 2009–2010. In vitro, the viruses from 2009–2010 also differed from the 2014–2015 viruses by increased release of infectious virus, a more pronounced loss of ciliated cells, and a reduced thickness of the epithelial cell layer. Our in vivo and in vitro results reveal an evolution of A(H1N1)pdm09 viruses toward lower virulence. Our in vitro culture system can be used to predict the virulence of influenza viruses.

Kun Su, Sheng Ye, Qin Li, Weijia Xie, Hongyue Yu, Li Qi, Yu Xiong, Han Zhao, Baisong Li, Hua Ling, Yun Tang, Bangzhong Xiao, Rong Rong, Wenge Tang, Yafei Li

Dunbar A, Schauwvlieghe A, Rijnders B.

Keer Sun, Dennis W. Metzger

Bacterial lung infections are frequent causes of mortality following influenza infection, but the fundamental mechanisms remain largely unknown. A new study by Martínez-Colón et al. (PLoS Pathog. 2019;15:e1007560) now suggests that influenza-induced immune suppression of Staphylococcus aureus is mediated by TLR9 signaling.

Feng Wen, Xiu-Feng Wan

Influenza virus neuraminidase cleaves sialic acid groups from cell glycoproteins, enabling release of the virus from host cells. Neuraminidase also contributes to virus binding to the sialic acid groups of cell glycoproteins, which could complement the receptor-binding function of hemagglutinin, enhancing enzymatic activities of neuraminidase, and facilitate virus infection.

Segaloff H, Leventer-Roberts M, Riesel D, et al.

AbstractBackgroundInfluenza vaccine effectiveness (VE) varies by season, circulating influenza strain, age, and geographic location. There have been few studies of influenza VE among hospitalized children, particularly in Europe and the Middle East. MethodsWe estimated VE against influenza hospitalization among children six months to eight years at Clalit Health Services hospitals in Israel in the 2015-16, 2016-17, and 2017-18 influenza seasons using the test-negative design. Estimates were computed for full and partial vaccination.ResultsWe included 326 influenza-positive cases and 2821 influenza-negative controls (140 cases and 971 controls from 2015-16, 36 cases and 1069 controls from 2016-17, and 150 cases and 781 controls from 2017-18). Over all seasons, VE was 53.9% for full vaccination (95% CI:(38.6,68.3)), and 25.6% for partial vaccination (95% CI:(-3, 47)). In 2015-16, most viruses were influenza A(H1N1) and vaccine lineage-mismatched influenza B/Victoria; VE for fully vaccinated children was statistically significant for influenza A (80.7%, 95% CI:(40.3,96.1)) but not B (23.0%, 95% CI:(-38.5, 59.4)). During 2016-17, influenza A(H3N2) predominated, and VE was (70.8%, 95% CI:(17.4, 92.4)). In 2017-18, influenza A(H3N2), H1N1 and lineage-mismatched influenza B/Yamagata co-circulated; VE was statistically significant for influenza B (63.0% 95% CI: (24.2,83.7)), but not A (46.3%, 95% CI:(-7.2, 75.3)).ConclusionsInfluenza vaccine was effective in preventing hospitalizations among fully vaccinated Israeli children over three influenza seasons, but not among partially vaccinated children. There was cross-lineage protection in a season where the vaccine contained B/Victoria and the circulating strain was B/Yamagata, but not in a season with the opposite vaccine-circulating strain distribution.

Rich, H. E., McCourt, C. C., Zheng, W. Q., McHugh, K. J., Robinson, K. M., Wang, J., Alcorn, J. F.

Influenza kills 30-40,000 people each year in the United States, and causes ten times as many hospitalizations. A common complication of influenza is bacterial super-infection, which exacerbates morbidity and mortality from the viral illness. Recently, MRSA has emerged as the dominant pathogen found in bacterial super-infection, with Streptococcus pneumoniae a close second. However, clinicians have few tools to treat bacterial super-infection. Current therapy for influenza/bacterial super-infection consists of treating the underlying influenza infection, adding various antibiotics which are increasingly rendered ineffective by rising bacterial multi-drug resistance. Several groups have recently proposed using the antiviral cytokine interferon lambda (IFN-) as a therapeutic for influenza, as administration of pegylated IFN- improves lung function and survival during influenza by reducing the overabundance of neutrophils in the lung. However, our data suggest that therapeutic IFN- impairs bacterial clearance during influenza super-infection. Specifically, mice treated with an adenoviral vector to overexpress IFN- during influenza infection exhibited increased bacterial burden upon super-infection with either MRSA or S. pneumoniae. Surprisingly, adhesion molecule expression, antimicrobial peptide production, and reactive oxygen species activity were not altered by IFN- treatment. However, neutrophil uptake of MRSA and S. pneumoniae was significantly reduced upon IFN- treatment during influenza super-infection in vivo. Together, these data support the theory that IFN- decreases neutrophil motility and function in the influenza-infected lung, which increases bacterial burden during super-infection. Thus, we believe caution should be exercised in the possible future use of IFN- as therapy for influenza.…

Qi Wang, Daining Zhang, Wenjing Feng, Yidi Guo, Xiaoning Sun, Maolin Zhang, Zhenhong Guan, Ming Duan

ABSTRACT Although the expression of thousands of host long noncoding RNAs (lncRNAs) can be regulated by viral infection, the number of lncRNAs with experimentally verified function is limited. In this study, the expression of host lncRNA TSPOAP1‐AS1 was significantly induced by influenza A virus (IAV) infection in a dose and time dependent manner. Poly (I:C), a synthetic analog of double‐stranded RNA, also increased TSPOAP1‐AS1 expression. RNA fractionation revealed that TSPOAP1‐AS1 was a nucleocytoplasmic lncRNA, and an increased nuclear/cytoplasmic ratio was detected after IAV infection. NF‐κB signaling acting as a critical factor in transcription of TSPOAP1‐AS1 was determined through the use of pharmacological and genetic approaches. Functionally, overexpression of TSPOAP1‐AS1 resulted in a significant increase in IAV replication. In contrast, abolition of TSPOAP1‐AS1 by RNA interference restricted viral replication. Furthermore, we demonstrated that TSPOAP1‐AS1 negatively modulated the IAV‐induced Ifnb1 transcription, ISRE activation and downstream ISG expression. Collectively, our data provides evidence for the host lncRNA utilized by viruses to support its replication. This article is protected by copyright. All rights reserved.

Kelly Lindert, Brett Leav, Esther Heijnen, Julia Barrett, Uwe Nicolay

Maysoon Bakri, Monjed Samuh, Maysa Azzeh

by Maysoon Bakri, Monjed Samuh, Maysa Azzeh Frequent typing and molecular characterization of influenza A (IAV) strains are crucial for the identification of circulating subtypes and for the selection of the subtypes’ lineages to be included in the annually prepared vaccine cocktail. We investigated IAV sampled from an underrepresented population from Palestine. 200 nasopharyngeal aspirates (NPA) were collected between February and May of 2015 from Palestinians in East Jerusalem and the West Bank suffering from mild to severe symptoms of upper respiratory infections. NPA were screened for the presence of IAV using RT-PCR. Epidemiological data, hemagglutinin (HA) and neuraminidase (NA) gene sequences were analyzed in IAV positive samples. 50 samples tested positive for IAV; 48% of which were identified as A(H1N1)pdm09 and 52% as A(H3N2), respectively. Infection with A(H1N1)pdm09 occurred mainly in April, while A(H3N2) infections were mainly detected in March. Most IAV infections in 6-year-olds and below were attributed to subtype A(H3N2), while A(H1N1)pdm09 was responsible for most infections in adults above 18-year-olds. Analyses of HA and NA amino acid sequences revealed numerous substitutions. Thereafter, and based on the HA analysis, the Palestinian A(H1N1)pdm09 isolates fell into clade 6B, while the A(H3N2) isolates fell into clades 3C.2 and 3C.3, respectively. This study is significant in providing the first insight into the epidemiology and genetic properties of IAV circulating in Palestine. In contrast to international reports for the same season, A(H3N2) was not the dominant subtype as in northern hemisphere, nor was A(H1N1)pdm09 as in WHO reports for the Middle East, however genetic properties of Palestinian A(H3N2) and A(H1N1)pdm09 were in line with global isolates.

Xiangqi Hao, Ruohan Liu, Yuwei He, Xiangyu Xiao, Weiqi Xiao, Qingxu Zheng, Xi Lin, Pan Tao, Pei Zhou, Shoujun Li

by Xiangqi Hao, Ruohan Liu, Yuwei He, Xiangyu Xiao, Weiqi Xiao, Qingxu Zheng, Xi Lin, Pan Tao, Pei Zhou, Shoujun Li Viral respiratory and intestinal infections are the most common causes of canine viral illness. Infection with multiple pathogens occurs in many cases. Rapid diagnosis of these multiple infections is important for providing timely and effective treatment. To improve diagnosis, in this study, two new multiplex polymerase chain reactions (mPCRs) were developed for simultaneous detection of canine respiratory viruses (CRV) and canine enteric viruses (CEV) using two separate primer mixes. The viruses included canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine influenza virus (CIV), canine parainfluenza virus (CPIV), canine circovirus (CanineCV), canine coronavirus (CCoV) and canine parvovirus (CPV). The sensitivity of the mPCR results showed that the detection limit of both mPCR methods was 1×104 viral copies. Twenty nasal swabs (NS) and 20 anal swabs (AS) collected from dogs with symptoms of respiratory disease or enteric disease were evaluated using the novel mPCR methods as a clinical test. The mPCR protocols, when applied to these respiratory specimens and intestinal samples, could detect 7 viruses simultaneously, allowing rapid investigation of CRV (CAV-2, CDV, CIV and CPIV) and CEV (CAV-2, CanineCV, CCoV and CPV) status and prompt evaluation of coinfection. Our study provides an effective and accurate tool for rapid differential diagnosis and epidemiological surveillance in dogs.