Influenza Surveillance Among Children With Pneumonia Admitted to a District Hospital in Coastal Kenya, 2007–2010

Abstract Background Influenza data gaps in sub-Saharan Africa include incidence, case fatality, seasonal patterns, and associations with prevalent disorders. Methods Nasopharyngeal samples from children aged <12 years who were admitted to Kilifi District Hospital during 2007–2010 with severe or very severe pneumonia and resided in the local demographic surveillance system were screened for influenza A, B, and C viruses by molecular methods. Outpatient children provided comparative data. Results Of 2002 admissions, influenza A virus infection was diagnosed in 3.5% (71), influenza B virus infection, in 0.9% (19); and influenza C virus infection, in 0.8% (11 of 1404 tested). Four patients with influenza died. Among outpatients, 13 of 331 (3.9%) with acute respiratory infection and 1 of 196 without acute respiratory infection were influenza positive. The annual incidence of severe or very severe pneumonia, of influenza (any type), and of influenza A, was 1321, 60, and 43 cases per 100 000 <5 years of age, respectively. Peak occurrence was in quarters 3–4 each year, and approximately 50% of cases involved infants: temporal association with bacteremia was absent. Hypoxia was more frequent among pneumonia cases involving influenza (odds ratio, 1.78; 95% confidence interval, 1.04–1.96). Influenza A virus subtypes were seasonal H3N2 (57%), seasonal H1N1 (12%), and 2009 pandemic H1N1 (7%). Conclusions The burden of influenza was small during 2007–2010 in this pediatric hospital in Kenya. Influenza A virus subtype H3N2 predominated, and 2009 pandemic influenza A virus subtype H1N1 had little impact.

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Broadly Cross-Reactive, Nonneutralizing Antibodies against Influenza B Virus Hemagglutinin Demonstrate Effector Function-Dependent Protection against Lethal Viral Challenge in Mice

Journal of Virology ◽

10.1128/jvi.01696-18 ◽

2019 ◽

Vol 93 (6) ◽

Cited By ~ 18

Author(s):

Guha Asthagiri Arunkumar ◽

Andriani Ioannou ◽

Teddy John Wohlbold ◽

Philip Meade ◽

Sadaf Aslam ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Mechanism Of Action ◽

Influenza A ◽

Effector Function ◽

Influenza B Virus ◽

Influenza B ◽

B Virus ◽

Protective Antibodies

ABSTRACT Protection from influenza virus infection is canonically associated with antibodies that neutralize the virus by blocking the interaction between the viral hemagglutinin and host cell receptors. However, protection can also be conferred by other mechanisms, including antibody-mediated effector functions. Here, we report the characterization of 22 broadly cross-reactive, nonneutralizing antibodies specific for influenza B virus hemagglutinin. The majority of these antibodies recognized influenza B viruses isolated over the period of 73 years and bind the conserved stalk domain of the hemagglutinin. A proportion of the characterized antibodies protected mice from both morbidity and mortality after challenge with a lethal dose of influenza B virus. Activity in an antibody-dependent cell-mediated cytotoxicity reporter assay correlated strongly with protection, suggesting that Fc-dependent effector function determines protective efficacy. The information regarding mechanism of action and epitope location stemming from our characterization of these antibodies will inform the design of urgently needed vaccines that could induce broad protection against influenza B viruses. IMPORTANCE While broadly protective antibodies against the influenza A virus hemagglutinin have been well studied, very limited information is available for antibodies that broadly recognize influenza B viruses. Similarly, the development of a universal or broadly protective influenza B virus vaccine lags behind the development of such a vaccine for influenza A virus. More information about epitope location and mechanism of action of broadly protective influenza B virus antibodies is required to inform vaccine development. In addition, protective antibodies could be a useful tool to treat or prevent influenza B virus infection in pediatric cohorts or in a therapeutic setting in immunocompromised individuals in conjugation with existing treatment avenues.

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Robust Lys63-Linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection

Journal of Virology ◽

10.1128/jvi.00549-16 ◽

2016 ◽

Vol 90 (14) ◽

pp. 6263-6275 ◽

Cited By ~ 17

Author(s):

Jingwen Jiang ◽

Jing Li ◽

Wenhui Fan ◽

Weinan Zheng ◽

Meng Yu ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Molecular Mechanisms ◽

Rna Binding ◽

Influenza B Virus ◽

Influenza B ◽

Type I ◽

Ns1 Protein ◽

B Virus

ABSTRACTInfluenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and proinflammatory factors can be induced by influenza B virus rather than influenza A virus infection in alveolar epithelial (A549) cells during early infection. This response is mainly dependent on the retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway. Infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25 and that this interaction blocks the inhibitory effect of the NS1-B C-terminal effector domain (TED) on RIG-I ubiquitination. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins.IMPORTANCEInfluenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response to influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus infection. Additionally, TRIM25 positively regulates RIG-I-mediated signaling by ablating the inhibitory function of NS1-B on RIG-I ubiquitination.

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Enhancement of the Influenza Surveillance System in the Russian Federation: the Main Results of the Sentinel Surveillance for Influenza and other Acute Respiratory Viral Infections

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2017-16-1-7-15 ◽

2017 ◽

Vol 16 (1) ◽

pp. 7-15 ◽

Cited By ~ 2

Author(s):

A. A. Sominina ◽

E. A. Smorodintseva ◽

K. A. Stolyarov ◽

A. A. Mel'nikova

Keyword(s):

Respiratory Infection ◽

Surveillance System ◽

Acute Respiratory Infection ◽

Influenza A ◽

Hospitalized Patients ◽

Sentinel Surveillance ◽

Influenza Surveillance ◽

Influenza B Virus ◽

Influenza B ◽

Influenza A H1n1

Existing influenza surveillance system is constantly improved to obtain comprehensive information for understanding of continuously changing situation with the influenza, which is a consequence of the highest variability of the pathogen, its ability to reassortment and the imminence of emergence a new shift-variants of the virus that could cause the next pandemic events. For this purpose, since the 2010 - 2011 epidemic season, in addition to the traditional surveillance system (TS) a new well standardized sentinel surveillance system (SS) for rapid clinical and epidemiological data obtaining was introduced in Russia. A total 7812 hospitalized patients with severe acute respiratory infection (SARI) and 9854 outpatients with influenza-like illness and acute respiratory infection (ILI/ARI) were investigated during the 6-year period in SS. Percent of SARI among all hospitalized patients ranged from 1.7 to 3.1%; about 5.3 - 7.5% SARI patients were placed in the Intensive Care Unit. Etiological monitoring using PCR showed influenza spread trends in SS similar to those registered in the TS: a clear predominance of influenza A (H1N1) pdm09 among SARI and ILI/ARI in 2010 - 2011 and 2015 - 2016 epidemic seasons, influenza A (H3N2) in the epidemic seasons 2011 - 2012 and 2014 - 2015, the co-circulation of these pathogens in 2012 - 2013, 2013 - 2014 seasons in Russia. SARI caused by influenza B virus were detected less frequently than influenza A but increased influenza B activity was registered in the epidemic of 2014 -2015, when Yamagata lineage changed suddenly for the Victorian one. The average frequency of influenza diagnosis among SARI between the seasons varied in the range 12.5 - 27.1%, at the peak of the epidemic it reached 44.8 - 73.5% and was the highest during the season with active circulation of influenza A (H1N1) pdm09 virus. The rate of influenza diagnosis among ILI/ARI has always been lower than that among SARI. Studies have also shown the importance of rhinovirus, RS-virus and parainfluenza infections in SARI development. The frequency of registration of coronaviruses, metapneumovirus and bocavirus infection was very low in SARI and ILI/ARI. It was found that in all studied seasons most of SARI patients with influenza have not been vaccinated. Among ILI/ARI outpatients with influenza, the frequency of vaccinated individuals for the entire period of the study was estimated as 10.1%, which was 4.2 times higher than that in SARI, where only 2.4% of patients were vaccinated. In addition, it was found that for all six seasons the SARI patients with influenza were treated with antivirals drugs 2 times less often compared to outpatients. Analysis of data on concomitant diseases and conditions in SARI patients with influenza confirmed the leading role of pregnancy as a risk factor for hospitalization in all influenza epidemics, irrespective of their etiology. In addition, diabetes and cardiovascular disease were recognized as risk factors for influenza associated SARI development.

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Epidemiological and clinical features of acute respiratory infections occurring in St. Petersburg during the 2017–2018 and 2018–2019 epidemic seasons

Journal Infectology ◽

10.22625/2072-6732-2021-13-2-53-60 ◽

2021 ◽

Vol 13 (2) ◽

pp. 53-60

Author(s):

D. A. Guzhov ◽

E. A. Elpaeva ◽

M. A. Egorova ◽

V. A. Eder ◽

I. L. Baranovskya ◽

...

Keyword(s):

Clinical Features ◽

Respiratory Infection ◽

Acute Respiratory Infection ◽

Influenza A ◽

Bacterial Infections ◽

Respiratory Infections ◽

Influenza B Virus ◽

Influenza B ◽

Acute Respiratory Infections ◽

Pharyngeal Wall

Objective: to analyze the epidemiological and clinical features of acute respiratory infections occurring during the St. Petersburg 2017-2018 and 2018-2019 epidemic seasons.Materials and methods: the study included 457 patients, treated in St. Petersburg clinics from 2017-2019, displaying symptoms of acute respiratory infection (ARI), including evaluation of their clinical histories. Pathogen types were determined by polymerase chain reaction (PCR). Data analysis was carried out using mathematical statistics methods using the Statistica 10 software package (StatSoft Inc.).Results: in this study, we examined the epidemiological and clinical features of acute respiratory infections in St. Petersburg occurring during two epidemic seasons, 2017-2018 and 2018-2019. The 2017-2018 season was characterized by a prevalence of infections caused by influenza B viruses and influenza A subtype H3N2 viruses. In the 2018-2019 season, there was a greater number of acute respiratory viral infections (ARVIs) and infections caused by influenza A subtype H1N1pdm; influenza B virus was detected only in isolated cases. In the 2017-2018 sore throats and muscle aches were a characteristic symptom of influenza A H1N1pdm infections, of bacterial infections – only sore throats. It was shown that throat pain and vasodilation of the scleral and soft palate vessels were significantly more frequent in the 2017-2018 season, compared to the 2018-2019 season. Cough and redness of the posterior pharyngeal wall were hallmark signs of ARVIs in the 2018-2019 season.Conclusion: according to the data, each epidemic season is characterized not only by its own type-specific acute respiratory infection frequencies, but also by different clinical manifestation frequencies. For global monitoring, treatment effectiveness evaluation, and refined study of acute respiratory infection clinical features, it is advisable to use approaches which incorporate accurate, specific, and rapid molecular biological methods capable of identifying a broad range of pathogens.

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Epidemiological and clinical features of acute respiratory infections occurring in St. Petersburg during the 2017–2018 and 2018–2019 epidemic seasons

Journal Infectology ◽

10.22625/2072-6732-2020-12-4-65-71 ◽

2020 ◽

Vol 12 (4) ◽

pp. 65-71

Author(s):

D. A. Guzhov ◽

E. A. Elpaeva ◽

M. A. Egorova ◽

V. A. Eder ◽

I. L. Baranovskaya ◽

...

Keyword(s):

Clinical Features ◽

Respiratory Infection ◽

Acute Respiratory Infection ◽

Influenza A ◽

Bacterial Infections ◽

Respiratory Infections ◽

Influenza B Virus ◽

Influenza B ◽

Acute Respiratory Infections ◽

Pharyngeal Wall

Objective: to analyze the epidemiological and clinical features of acute respiratory infections occurring during the St. Petersburg 2017–2018 and 2018–2019 epidemic seasons.Materials and methods: the study included 457 patients, treated in St. Petersburg clinics from 2017–2019, displaying symptoms of acute respiratory infection (ARI), including evaluation of their clinical histories. Pathogen types were determined by polymerase chain reaction (PCR). Data analysis was carried out using mathematical statistics methods using the Statistica 10 software package (StatSoft Inc.).Results: in this study, we examined the epidemiological and clinical features of acute respiratory infections in St. Petersburg occurring during two epidemic seasons, 2017–2018 and 2018–2019. The 2017–2018 season was characterized by a prevalence of infections caused by influenza B viruses and influenza A subtype H3N2 viruses. In the 2018–2019 season, there was a greater number of acute respiratory viral infections (ARVIs) and infections caused by influenza A subtype H1N1pdm; influenza B virus was detected only in isolated cases. In the 2017–2018 sore throats and muscle aches were a characteristic symptom of influenza A H1N1pdm infections, of bacterial infections – only sore throats. It was shown that throat pain and vasodilation of the scleral and soft palate vessels were significantly more frequent in the 2017–2018 season, compared to the 2018–2019 season. Cough and redness of the posterior pharyngeal wall were hallmark signs of ARVIs in the 2018–2019 season.Conclusion: according to the data, each epidemic season is characterized not only by its own type-specific acute respiratory infection frequencies, but also by different clinical manifestation frequencies. For global monitoring, treatment effectiveness evaluation, and refined study of acute respiratory infection clinical features, it is advisable to use approaches which incorporate accurate, specific, and rapid molecular biological methods capable of identifying a broad range of pathogens.

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Acute Respiratory Disease at a Chinese Military Recruitment Training Center: Three-Year Consecutive Investigation

Infection International ◽

10.1515/ii-2017-0084 ◽

2014 ◽

Vol 3 (3) ◽

pp. 108-113

Author(s):

Jun-fei Zhang ◽

Jian Fang ◽

Hai-yan Song ◽

Wei-li Wu ◽

Bo Liu ◽

...

Keyword(s):

Virus Infection ◽

Respiratory Disease ◽

Influenza A Virus ◽

Legionella Pneumophila ◽

Influenza A ◽

Influenza B Virus ◽

Influenza B ◽

Training Center ◽

Acute Respiratory Disease ◽

B Virus

Abstract Background Military recruits are at a higher risk of acute respiratory disease (ARD) and the causative agents might change over time, which needs to be investigated. Methods The nasopharyngeal swabs and blood samples were consecutively collected from conscripts for three years in a military training center. The real-time fluorescent quantitative PCR assays were conducted for 15 species of common respiratory pathogens; the serum anti-Legionella pneumophila antibodies were detected by indirect immunofluorescence (IIF) assay, and serum anti-Microplasma pneumoniae antibodies, serum anti-influenza B virus and anti-influenza A virus-IgM and IgG were detected by ELISA. Results The prevalences of ARD were 59.3% (108/182) in 2008, 23.3% (50/215) in 2009, and 19.6% (40/204) in 2010. Among the patients with ARD from 2008 to 2010, the influenza B virus infection accounted for 45.4%, 30.0% and 55.0%, and seasonal influenza A virus infection for 8.3%, 8.0% and 5.0%, respectively; the positive rates of serum anti-Legionella pneumophila and anti-Microplasma pneumoniae antibodies in recruits was lower than 10% each year respectively in the three years without diagnostic significance. Conclusion The early appropriate diagnosis and treatment of ARD in military personnel will ensure the power strength of armed forces.

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RIG-I Signaling Is Essential for Influenza B Virus-Induced Rapid Interferon Gene Expression

Journal of Virology ◽

10.1128/jvi.01576-15 ◽

2015 ◽

Vol 89 (23) ◽

pp. 12014-12025 ◽

Cited By ~ 25

Author(s):

Sanna M. Mäkelä ◽

Pamela Österlund ◽

Veera Westenius ◽

Sinikka Latvala ◽

Michael S. Diamond ◽

...

Keyword(s):

Gene Expression ◽

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Innate Immune ◽

Influenza B Virus ◽

Influenza B ◽

Immune Recognition ◽

B Virus ◽

Irf3 Activation

ABSTRACTInfluenza B virus causes annual epidemics and, along with influenza A virus, accounts for substantial disease and economic burden throughout the world. Influenza B virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza A virus. Influenza B virus has been less studied than influenza A virus, and thus, a comparison of influenza A and B virus infection mechanisms may provide new insight into virus-host interactions. Here we analyzed the early events in influenza B virus infection and interferon (IFN) gene expression in human monocyte-derived macrophages and dendritic cells. We show that influenza B virus induces IFN regulatory factor 3 (IRF3) activation and IFN-λ1 gene expression with faster kinetics than does influenza A virus, without a requirement for viral protein synthesis or replication. Influenza B virus-induced activation of IRF3 required the fusion of viral and endosomal membranes, and nuclear accumulation of IRF3 and viral NP occurred concurrently. In comparison, immediate early IRF3 activation was not observed in influenza A virus-infected macrophages. Experiments with RIG-I-, MDA5-, and RIG-I/MDA5-deficient mouse fibroblasts showed that RIG-I is the critical pattern recognition receptor needed for the influenza B virus-induced activation of IRF3. Our results show that innate immune mechanisms are activated immediately after influenza B virus entry through the endocytic pathway, whereas influenza A virus avoids early IRF3 activation and IFN gene induction.IMPORTANCERecently, a great deal of interest has been paid to identifying the ligands for RIG-I under conditions of natural infection, as many previous studies have been based on transfection of cells with different types of viral or synthetic RNA structures. We shed light on this question by analyzing the earliest step in innate immune recognition of influenza B virus by human macrophages. We show that influenza B virus induces IRF3 activation, leading to IFN gene expression after viral RNPs (vRNPs) are released into the cytosol and are recognized by RIG-I receptor, meaning that the incoming influenza B virus is already able to activate IFN gene expression. In contrast, influenza A (H3N2) virus failed to activate IRF3 at very early times of infection, suggesting that there are differences in innate immune recognition between influenza A and B viruses.

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The cellular immunophenotype expression of influenza A virus and influenza B virus infection in children

Clinical Immunology ◽

10.1016/j.clim.2020.108548 ◽

2020 ◽

Vol 219 ◽

pp. 108548 ◽

Cited By ~ 1

Author(s):

Ching-Fen Shen ◽

Tzong-Shiann Ho ◽

Shih-Min Wang ◽

Yu-Ting Liao ◽

Yu-Shiang Hu ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Influenza B Virus ◽

Influenza B ◽

B Virus

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QUALITATIVE DIFFERENCES IN THE ANTIGENIC COMPOSITION OF INFLUENZA A VIRUS STRAINS

Journal of Experimental Medicine ◽

10.1084/jem.79.6.633 ◽

1944 ◽

Vol 79 (6) ◽

pp. 633-647 ◽

Cited By ~ 18

Author(s):

William F. Friedewald

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Serum Antibody ◽

Allantoic Fluid ◽

Influenza B Virus ◽

Influenza B ◽

Red Cell ◽

Homologous Virus ◽

Cell Adsorption ◽

Virus Strains

A study of the PR8, Christie, Talmey, W.S., and swine strains of influenza A virus by means of antibody absorption tests revealed the following findings: 1. Serum antibody could be specifically absorbed with allantoic fluid containing influenza virus or, more effectively, with concentrated suspensions of virus obtained from allantoic fluid by high-speed centrifugation or by the red cell adsorption and elution technique. Normal allantoic fluid, or the centrifugalized sediment therefrom, failed to absorb antibodies. Influenza B virus (Lee) caused no detectable absorption of antibody from antisera directed against influenza A virus strains, but it specifically absorbed antibody from Lee antisera. 2. The neutralizing, agglutination-inhibiting, and complement-fixing anti-bodies in ferret antisera were completely absorbed only by the homologous virus strain, even though 2 absorptions were carried out with large amounts of heterologous virus strains. 3. PR8 virus appeared to have the broadest range of specific antigenic components for it completely absorbed the heterologous antibodies in Christie and W.S. antisera and left only those antibodies which reacted with the respective homologous strains. The other virus strains (Christie, Talmey, W.S., swine) were more specific in the absorption of heterologous antibodies and completely removed only those antibodies which reacted with the absorbing virus. 4. The absorption tests revealed a higher degree of specificity and individuality of the virus strains than the various cross reactions previously reported. The strain specificity of PR8 virus was equally manifest in absorption tests with ferret sera and with human sera following vaccination. 5. The amount of homologous antibody remaining in a PR8 ferret serum after absorption with PR8 virus, obtained by the red cell adsorption and elution method, varied inversely as the concentration of virus used for absorption. A given concentration of virus, however, absorbed a greater percentage of neutralizing antibodies than either agglutination-inhibiting or complement-fixing antibodies.

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