Severe Influenza Virus Infection in Children Admitted to the PICU: Comparison of Influenza A and Influenza B Virus Infection

Author(s):  
Pınar YAZICI ÖZKAYA ◽  
Eşe Eda TURANLI ◽  
Hamdi METİN ◽  
Ayça Aydın UYSAL ◽  
Candan ÇİÇEK ◽  
...  
mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Mira C. Patel ◽  
Kari Ann Shirey ◽  
Marina S. Boukhvalova ◽  
Stefanie N. Vogel ◽  
Jorge C. G. Blanco

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.


2020 ◽  
Vol 43 (3) ◽  
pp. 1-7
Author(s):  
Nattapol Narong ◽  
Siriwat Manajit ◽  
Sirikarn Athipanyasil ◽  
Niracha Athipanyasilp ◽  
Ruengpung Sutthent ◽  
...  

Background: Influenza A (pandemic and seasonal H1/H3) and influenza B viruses were the predominant circulating seasonal influenza strains. Following its massive outbreak in 2009 globally, including Thailand, influenza A (H1N1) pdm09 viruses have replaced the previous seasonal H1 strain and become one of the circulating strains ever since. Both influenza A and B viruses are highly contagious and potentially cause respiratory illness ranging from mild to severe. Objective: To determine the prevalence of types and subtypes of circulating influenza virus strains in Bangkok, Thailand during 2013 - 2017. Methods: The 4385 nasopharyngeal wash specimens were collected from patients presented with influenza-like illness from January 2013 to December 2017 at Siriraj Hospital, Bangkok, Thailand. Influenza virus types and subtypes were determined using real-time RT-PCR technique. Clinical characteristics of patients infected with influenza A viruses and influenza B virus were compared and analyzed. Results: Of 4385 nasopharyngeal wash specimens, the prevalence of influenza virus infection during 2013 - 2017 was 18.22% (n = 799). Of 799 influenza-positive samples, 608 (76.09%) and 191 (23.90%) samples were positive for influenza A and influenza B viruses, respectively. Most patients were presented with fever, cough, and runny nose; however, patients infected with influenza A virus generally had higher severity than those with influenza B virus infection (P < .05). Conclusions: The findings provided the characteristics of influenza virus types and subtypes at Siriraj Hospital, Bangkok, Thailand during 2013 - 2017. Sporadic cases of influenza occurred all year round, but the incidence peaked in March 2014 and August 2017. The outcomes of this study are potentially useful for prevention, treatment, and disease monitoring.  


1948 ◽  
Vol 88 (3) ◽  
pp. 343-353 ◽  
Author(s):  
William F. Friedewald ◽  
Edward W. Hook

A study of influenza virus infection in the hamster has yielded the following results: 1. Two influenza A strains (Ga. 47 and PR8) multiplied readily in the hamster lung, although no lung lesions were produced during six serial passages. On further passage both viruses abruptly acquired the capacity to produce pulmonary consolidation and death of the animals. 2. Extracts of the lungs during the early passages contained complement-fixing antigen and infectious virus, as revealed by titration in mice and embryonated eggs. Agglutinins for chicken, human, and guinea pig red cells, however, were not demonstrable at this time. With further passage a close correlation was observed between the capacity of the virus to produce lung lesions in the hamster and to agglutinate mammalian types of red cells. In addition, quantitative changes in the virus population were demonstrated in the lung extracts by complement fixation tests and titrations in mice and eggs. 3. Incubation at 37°C. was effective in bringing out agglutinins in high titer for chicken red cells in lung extracts, which originally failed to agglutinate chicken cells but agglutinated mammalian red cells. This method did not increase the titers of mammalian cell agglutinins. 4. The body temperature of the hamster was found to decrease within 1 to 4 days after inoculation of influenza virus. In the early passages the temperature returned to normal within 24 hours, but with the development of the pathogenic strain of virus the temperature remained at subnormal levels until death. 5. The Lee strain of influenza B virus produced pulmonary lesions in the hamster on the first passage and no increase in pathogenicity of the virus occurred during eleven serial passages. Virus was demonstrable in extracts of the lungs by all the methods used and no difference was observed in its capacity to agglutinate fowl and mammalian types of red cells. The implications of these findings are considered briefly in the discussion.


2020 ◽  
Vol 94 (7) ◽  
Author(s):  
Sook-San Wong ◽  
Ben Waite ◽  
Jacqui Ralston ◽  
Tim Wood ◽  
G. Edwin Reynolds ◽  
...  

ABSTRACT Despite evidence that antibodies targeting the influenza virus neuraminidase (NA) protein can be protective and are broadly cross-reactive, the immune response to NA during infection is poorly understood compared to the response to hemagglutinin (HA) protein. As such, we compared the antibody profile to HA and NA in two naturally infected human cohorts in Auckland, New Zealand: (i) a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR-confirmed influenza cases (n = 50), and (ii) an immunology cohort, consisting of paired sera collected after PCR-confirmation of infection (n = 94). The induction of both HA and NA antibodies in these cohorts was influenced by age and subtype. Seroconversion to HA was more frequent in those <20 years old (yo) for influenza A (serosurvey, P = 0.01; immunology, P = 0.02) but not influenza B virus infection. Seroconversion to NA was not influenced by age or virus type. Adults ≥20 yo infected with influenza A viruses were more likely to show NA-only seroconversion compared to children (56% versus 14% [5 to 19 yo] and 0% [0 to 4 yo], respectively). Conversely, children infected with influenza B viruses were more likely than adults to show NA-only seroconversion (88% [0 to 4 yo] and 75% [5 to 19 yo] versus 40% [≥20 yo]). These data indicate a potential role for immunological memory in the dynamics of HA and NA antibody responses. A better mechanistic understanding of this phenomenon will be critical for any future vaccines aimed at eliciting NA immunity. IMPORTANCE Data on the immunologic responses to neuraminidase (NA) is lacking compared to what is available on hemagglutinin (HA) responses, despite growing evidence that NA immunity can be protective and broadly cross-reactive. Understanding these NA responses during natural infection is key to exploiting these properties for improving influenza vaccines. Using two community-acquired influenza cohorts, we showed that the induction of both HA and NA antibodies after infection is influenced by age and subtypes. Such response dynamics suggest the influence of immunological memory, and understanding how this process is regulated will be critical to any vaccine effort targeting NA immunity.


2020 ◽  
Vol 245 (18) ◽  
pp. 1664-1671
Author(s):  
Kritsada Khongnomnan ◽  
Suthat Saengchoowong ◽  
Oraphan Mayuramart ◽  
Pattaraporn Nimsamer ◽  
Trairak Pisitkun ◽  
...  

Influenza B virus is a member of the Orthomyxoviridae family which can infect humans and causes influenza. Although it is not pandemic like influenza A virus, it nevertheless affects millions of people worldwide annually. MicroRNAs are small non-coding RNAs regulating gene expression at posttranscriptional level. They play various important roles in cellular processes including response to viral infection. MiRNA profiles from our previous study suggested that miR-30e-3p was one of the upregulated miRNAs that responded to influenza B virus infection. In this study, in silico prediction and in vitro investigation proved that this miRNA can directly target NA and NP genes of the influenza B virus and inhibit its replication. This finding might be useful for using miRNA as an alternative therapeutics for influenza virus infection.


1999 ◽  
Vol 67 (6) ◽  
pp. 3082-3086 ◽  
Author(s):  
Robert C. Read ◽  
Linda Goodwin ◽  
M. Andrew Parsons ◽  
Paul Silcocks ◽  
Edward B. Kaczmarski ◽  
...  

ABSTRACT There is an epidemiological association between influenza virus infection and meningococcal disease. Proposed mechanisms are the destruction of the normal epithelial barrier function of the upper respiratory tract by influenza virus or the expression of human or viral surface-exposed proteins that enhance bacterial adherence and/or invasion. To test these hypotheses, human nasopharyngeal mucosa specimens from a total of 19 individual donors were successfully infected with influenza B virus and then inoculated with serogroup B Neisseria meningitidis. Subsequent bacterial association with the epithelial surface was measured in three separate series of experiments by using transmission electron microscopy (n = 6), scanning electron microscopy (n = 6), and counting of viable bacteria within homogenates of explants (n = 7). Penetration of the mucosa was estimated by measuring the count of viable bacteria recovered from explants after exposure to sodium taurocholate. Bacterial association with the surface of explants was time dependent over 24 h of superinfection. Influenza virus did not positively or negatively influence bacterial attachment to or penetration of explant mucosa compared to those of uninfected controls, even when the period of preincubation with virus was extended to 7 days. When proteins were purified from mucosal epithelium and immobilized on nitrocellulose membranes, N. meningitidis attached predominantly to bands corresponding to proteins of 210 and 130 kDa. In the presence of influenza virus infection, these proteins were gradually lost over the course of 72 h. In conclusion, influenza B virus did not increase association of serogroup B N. meningitidis with human nasopharyngeal mucosa.


2020 ◽  
Vol 15 (7) ◽  
pp. 441-453
Author(s):  
Ana Vazquez-Pagan ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.


1978 ◽  
Vol 80 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. Masurel ◽  
J. I. de Bruijne ◽  
H. A. Beuningh ◽  
H. J. A. Schouten

SUMMARYHaemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970–1.A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests.It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.


2020 ◽  
pp. 153537022096379
Author(s):  
Oraphan Mayuramart ◽  
Pattaraporn Nimsamer ◽  
Somruthai Rattanaburi ◽  
Naphat Chantaravisoot ◽  
Kritsada Khongnomnan ◽  
...  

Due to the common symptoms of COVID-19, patients are similar to influenza-like illness. Therefore, the detection method would be crucial to discriminate between SARS-CoV-2 and influenza virus-infected patients. In this study, CRISPR-Cas12a-based detection was applied for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus which would be a practical and attractive application for screening of patients with COVID-19 and influenza in areas with limited resources. The limit of detection for SARS-CoV-2, influenza A, and influenza B detection was 10, 103, and 103 copies/reaction, respectively. Moreover, the assays yielded no cross-reactivity against other respiratory viruses. The results revealed that the detection of influenza virus and SARS-CoV-2 by using RT-RPA and CRISPR-Cas12a technology reaches 96.23% sensitivity and 100% specificity for SARS-CoV-2 detection. The sensitivity for influenza virus A and B detections was 85.07% and 94.87%, respectively. In addition, the specificity for influenza virus A and B detections was approximately 96%. In conclusion, the RT-RPA with CRISPR-Cas12a assay was an effective method for the screening of influenza viruses and SARS-CoV-2 which could be applied to detect other infectious diseases in the future.


2019 ◽  
Vol 220 (6) ◽  
pp. 961-968 ◽  
Author(s):  
Tatiana Schäffer Gregianini ◽  
Ivana R Santos Varella ◽  
Patricia Fisch ◽  
Letícia Garay Martins ◽  
Ana B G Veiga

Abstract Influenza surveillance is important for disease control and should consider possible coinfection with different viruses, which can be associated with disease severity. This study analyzed 34 459 patients with respiratory infection from 2009 to 2018, of whom 8011 were positive for influenza A virus (IAV) or influenza B virus (IBV). We found 18 cases of dual influenza virus infection, including coinfection with 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) and influenza A(H3N2) virus (1 case), A(H1N1)pdm09 and IBV (6 cases), A(H3N2) and IBV (8 cases), and nonsubtyped IAV and IBV (3 cases); and 1 case of triple infection with A(H3N2), A(H1N1)pdm09, and IBV. Compared with 76 monoinfected patients, coinfection was significantly associated with cardiopathy and death. Besides demographic characteristics and clinical symptoms, we assessed vaccination status, antiviral treatment, timeliness of antiviral use, hospitalization, and intensive care unit admission, but no significant differences were found between coinfected and monoinfected cases. Our findings indicate that influenza virus coinfection occurs more often than previously reported and that it can lead to a worse disease outcome.


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