#Hemagglutinin and #neuraminidase #antibodies are induced in an #age- and subtype- dependent manner after #influenza virus infection (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Hemagglutinin and neuraminidase antibodies are induced in an age- and subtype- dependent manner after influenza virus infection.

Sook-San Wong, Ben Waite, Jacqui Ralston, Tim Wood, G Edwin Reynolds, Ruth Seeds, E. Claire Newbern, Mark G. Thompson, Q. Sue Huang, Richard J. Webby, the SHIVERS Investigation Team

DOI: 10.1128/JVI.01385-19



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; a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR-confirmed influenza cases (n=50), and 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% vs 14% [5 – 19 yo] and 0% [0 – 4 yo] respectively). Conversely, children infected with influenza B viruses were more likely than adults to show NA-only seroconversion (88% [0 – 4 yo] and 75% [5 – 19 yo] vs 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.



Data on the immunologic responses to neuraminidase (NA) is lacking when 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-antibody after infection is influenced by age and subtypes. Such response dynamics suggests the influence of immunological memory and understanding how this process is regulated will be critical to any vaccine effort targeting NA-immunity.

Copyright © 2020 Wong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Seasonal Influenza; Serology; Seroprevalence.


Comparison of alpha-spending plans for near #realtime #monitoring for #GBS after #influenza #vaccination during the 2010/11 influenza season (Vaccine, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vaccine. 2020 Jan 10. pii: S0264-410X(19)31674-3. doi: 10.1016/j.vaccine.2019.12.032. [Epub ahead of print]

Comparison of alpha-spending plans for near real-time monitoring for Guillain-Barré after influenza vaccination during the 2010/11 influenza season.

Sandhu SK1, Hua W2, MaCurdy TE3, Franks RL4, Avagyan A4, Chillarige Y4, Wernecke M4, Kelman J5, Ball R2.

Author information: 1 Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: sukhminder.sandhu@fda.hhs.gov. 2 Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 3 Stanford University, Stanford, CA, USA; Acumen LLC, Burlingame, CA, USA. 4 Acumen LLC, Burlingame, CA, USA. 5 Centers for Medicare and Medicaid Services, Washington, DC, USA.




Near real-time surveillance of the influenza vaccine, which is administered to a large proportion of the US population every year, is essential to ensure safety of the vaccine. For efficient near real-time surveillance, it is key to select appropriate parameters such as monitoring start date, number of interim tests and a scheme for spending a pre-defined total alpha across the entire influenza season. Guillain-Barré Syndrome, shown to be associated with the 1976 influenza vaccine, is used to evaluate how choices of these parameters can affect whether or not a signal is detected and the time to signal. FDA has been monitoring for the risk of GBS after influenza vaccination for every influenza season since 2008.


Using Medicare administrative data and the Updating Sequential Probability Ratio Test methodology to account for claims delay, we evaluated a number of different alpha-spending plans by varying several parameters.


For relative risks of 5 or greater, almost all alpha-spending plans have 100% power; however, for relative risks of 1.5 or lower, the constant and O’Brien-Fleming plans have increasingly more power. For RRs of 1.5 and greater, the Pocock plan signals earliest but would not signal at a RR of 1.25, as observed in prior influenza seasons. There were no remarkable differences across the different plans in regards to monitoring start dates defined by the number of vaccinations; reducing the number of interim tests improves performance only marginally.


A constant alpha-spending plan appears to be robust, in terms of power and time to detect a signal, across a range of these parameters, including alternate monitoring start dates based on either cumulative vaccinations or GBS claims observed, frequency of monitoring, hypothetical relative risks, and vaccine uptake patterns.

Published by Elsevier Ltd.

KEYWORDS: Alpha-spending; Guillain-Barré Syndrome; Immunization; Influenza; Sequential test; Vaccine

PMID: 31932134 DOI: 10.1016/j.vaccine.2019.12.032

Keywords: Drugs safety; Seasonal Influenza; Vaccines; GBS.


Early Administration of #Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the #Risk of Influenza B Virus-Associated #Pneumonia in Hospitalized #Pediatric Patients with Influenza B Virus Infection (Pediatr Infect Dis J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pediatr Infect Dis J. 2020 Feb;39(2):e20-e22. doi: 10.1097/INF.0000000000002528.

Early Administration of Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the Risk of Influenza B Virus-Associated Pneumonia in Hospitalized Pediatric Patients with Influenza B Virus Infection.

Dai Z1, Zhang L, Yu Q, Liu L, Yang M, Fan K.

Author information: 1 From the Department of Accident and Emergency, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.



We conducted a retrospective study to identify the risk factors for pneumonia in hospitalized pediatric patients with influenza B infection. Receiving oseltamivir within the first 48 hours of onset and frequent cough was respectively considered as a protective factor and a risk factor for the influenza B virus-associated pneumonia in hospitalized pediatric patients. Early administration of oseltamivir can reduce the risk of influenza B virus-associated pneumonia.

PMID: 31929434 DOI: 10.1097/INF.0000000000002528

Keywords: Seasonal Influenza; Influenza B; Antivirals; Oseltamivir; Pneumonia; Pediatrics.


#Necrotizing #tracheobronchitis causing airway obstruction complicated by #H1N1pdm09 #influenza: A case report (Medicine (Baltimore), abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Medicine (Baltimore). 2020 Jan;99(1):e18647. doi: 10.1097/MD.0000000000018647.

Necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza: A case report.

Chang J1, Kim TO2, Yoon JY2, Kho BG2, Shin HJ2, Kwon YS2, Kim YI2, Lim SC2.

Author information: 1 Department of Internal Medicine, Mokpo Hankook Hospital, Jeollanamdo. 2 Department of Pulmonology and Critical Care Medicine, Chonnam National University Hospital, Gwangju, South Korea.




Influenza is an infection caused by the influenza virus, and its symptoms are mostly mild and self-limiting. However, influenza can cause severe or fatal complications in high-risk patients. Although tracheobronchitis is one of the common complications of influenza, necrotizing tracheobronchitis is very rare. Herein, we describe a case of necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza.


A 60-year-old man presented with fever and dyspnea. On arrival at the emergency room (ER), the patient received oxygen 4 L/minute via a nasal prolong owing to mild hypoxemia. And invasive mechanical ventilation was needed 5 hours after arrival at the ER due to progressive hypoxemia.


Fiberoptic bronchoscopy was performed owing to bloody secretion in the endotracheal tube and revealed diffuse tracheobronchitis with necrotic and hemorrhagic materials obstructing the trachea and bronchus. The pandemic 2009 H1N1 influenza virus was detected from the bronchial washing sample; no other microorganism was detected.


He received peramivir plus oseltamivir and broad-spectrum antibiotics.


The bloody secretion continued. He developed cardiac arrest due to airway obstruction on the 6th day of admission. After cardiac arrest, his condition progressed to multi-organ failure, and the patient died on the 10th day of admission.


We suggest that necrotizing tracheobronchitis be considered in patients with influenza who present with unexplained hypoxemia.

PMID: 31895828 DOI: 10.1097/MD.0000000000018647

Keywords: Seasonal Influenza; H1N1pdm09; Tracheobronchitis.


Severe #myocarditis due to #influenza A #H1N1pdm09 viral #infection in a young woman successfully treated with intravenous #zanamivir: A case report (Clin Case Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Case Rep. 2019 Oct 21;7(12):2336-2340. doi: 10.1002/ccr3.2499. eCollection 2019 Dec.

Severe myocarditis due to influenza A(H1N1)pdm09 viral infection in a young woman successfully treated with intravenous zanamivir: A case report.

Mazzitelli M1, Garofalo E2, Bruni A2, Barreca GS3, Quirino A3, Giancotti A3, Serapide F1, Indolfi C4, Matera G3, Navalesi P2, Trecarichi EM1, Torti C1, Longhini F2; IMAGES (Integrated MAnaGEment of Sepsis) Group.

Collaborators (16): Peronace C, Pisani V, Costa C, Greco G, La Gamba V, Scaglione V, Biamonte E, Brescia V, De Leonardis B, Karim A, Cimino G, La Torre P, Gemelli A, Tropea FA, Picicco F, Gallo L.

Author information: 1 Department of Medical and Surgical Sciences, Infectious and Tropical Diseases Unit “Magna Graecia” University Catanzaro Italy. 2 Department of Medical and Surgical Sciences Unit of Intensive Care, “Magna Graecia” University Catanzaro Italy. 3 Department of Health Sciences Unit of Clinical Microbiology “Magna Graecia” University Catanzaro Italy. 4 Department of Medical and Surgical Sciences Division of cardiology “Magna Graecia” University Catanzaro Italy.



In patients with influenza-related myocarditis, prompt diagnosis and treatment are important. Intravenous zanamivir can be an alternative to oral oseltamivir, especially in severe cases and when drug intestinal malabsorption is suspected or proven.

© 2019 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.

KEYWORDS: influenza A(H1N1)pdm09 virus; intravenous zanamivir; myocarditis

PMID: 31893053 PMCID: PMC6935647 DOI: 10.1002/ccr3.2499

Keywords: Influenza A; H1N1pdm09; Myocarditis; Antivirals; Zanamivir.


#Clinical #Features of Fatal Pandemic #Influenza A/ #H1N1 #Infection Complicated by Invasive #Pulmonary #Fungal Infection (Mycopathologia, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Mycopathologia. 2019 Dec 27. doi: 10.1007/s11046-019-00421-z. [Epub ahead of print]

Clinical Features of Fatal Pandemic Influenza A/H1N1 Infection Complicated by Invasive Pulmonary Fungal Infection.

Yu Z1, Gu Q1, Zhang B1, Chen X1, Tang J1, Hou Y1, Yu W2.

Author information: 1 Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, China. 2 Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, China. yudrnj@163.com.




Severe pneumonia caused by influenza virus infection can be secondary to invasive pulmonary fungal (IPF) infection.


This study aimed to summarize the incidence of IPF infection secondary to influenza virus infection and further explore its etiologic mechanism and high-risk factors.


All adult patients with confirmed influenza A (H1N1) virus infection admitted to the intensive care units (ICUs) of Nanjing Drum Hospital from November 2017 to March 2018 were retrospectively selected. The differences in baseline factors, risk factors, immune function and outcome parameters were studied between patients with and without IPF.


Of the 19 critically ill patients with H1N1 infection, 11 (57.9%) developed IPF infection after 7 days of ICU admission. Two patients had proven and nine probable IPF infection. A difference in human leukocyte antigen-DR isotype (△HLA-DR; day 7-day 1) was found between the two groups. △HLA-DR (day 7-day 1) was higher in patients with no IPF infection than in those with IPF infection [(14.52 ± 14.21)% vs ( - 11.74 ± 20.22)%, P = 0.019]. The decline in HLA-DR indicated impaired immune function secondary to fungal infection in patients with H1N1 infection.


IPF infection was diagnosed in 57.9% of critically ill patients with H1N1 virus infection after a median of 7 days following ICU admission. A continuous decline in immune function could lead to the development of IPF infections. Dynamic monitoring of immune function may help in the early detection of IPF infection.

KEYWORDS: H1N1; Human leukocyte antigen-DR isotype (HLA-DR); Invasive pulmonary fungal infection; Severe pneumonia

PMID: 31883036 DOI: 10.1007/s11046-019-00421-z

Keywords: Seasonal Influenza; Fungal infections; Pneumonia; SARI.


Association between #vaccine #adjuvant effect and pre-seasonal #immunity. Systematic review and meta-analysis of randomised immunogenicity trials comparing squalene-adjuvanted and aqueous inactivated #influenza vaccines (Vaccine, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vaccine. 2019 Dec 23. pii: S0264-410X(19)31679-2. doi: 10.1016/j.vaccine.2019.12.037. [Epub ahead of print]

Association between vaccine adjuvant effect and pre-seasonal immunity. Systematic review and meta-analysis of randomised immunogenicity trials comparing squalene-adjuvanted and aqueous inactivated influenza vaccines.

Beyer WEP1, Palache AM2, Reperant LA3, Boulfich M4, Osterhaus ADME5.

Author information: 1 Artemis One Health, Utrecht, the Netherlands; Erasmus Medical Center, Department of Viroscience, Rotterdam, the Netherlands. 2 FluPal Consultancy, Amstelveen, the Netherlands. 3 Artemis One Health, Utrecht, the Netherlands. 4 University of Amsterdam, the Netherlands. 5 Artemis One Health, Utrecht, the Netherlands; University of Veterinary Medicine, Hannover, Germany. Electronic address: Albert.Osterhaus@tiho-hannover.de.



The immunogenicity benefit of inactivated influenza vaccine (IIV) adjuvanted by squalene over non-adjuvanted aqueous IIV was explored in a meta-analysis involving 49 randomised trials published between 1999 and 2017, and 22,470 eligible persons of all age classes. Most vaccines contained 15 μg viral haemagglutinin per strain. Adjuvanted IIV mostly contained 9.75 mg squalene per dose. Homologous pre- and post-vaccination geometric mean titres (GMTs) of haemagglutination-inhibition (HI) antibody were recorded for 290 single influenza (sub-)type arms. The adjuvant effect was expressed as the ratio of post-vaccination GMTs between squalene-IIV and aqueous IIV (GMTR, 145 estimates). GMTRs > 1.0 favoured squalene-IIV over aqueous IIV. For all influenza (sub-)types, the adjuvant effect proved negatively associated with pre-vaccination GMT and mean age. The adjuvant effect appeared most pronounced in young children (mean age < 2.5 years) showing an average GMTR of 3.7 (95% CI: 2.5 to 5.5). With increasing age, GMTR values gradually decreased towards 1.4 (95% CI: 1.0 to 1.9) in older adults. Heterologous antibody titrations simulating mismatch between vaccine and circulating virus (30 GMTR estimates) again showed a larger adjuvant effect at young age. GMT values and their variances were converted to antibody-predicted protection rates using an evidence-based clinical protection curve. The adjuvant effect was expressed as the protection rate differences, which showed similar age patterns as corresponding GMTR values. However for influenza B, the adjuvant effect lasted longer than for influenza A, possibly due to a generally later influenza B virus exposure. Collectively, this meta-analysis indicates the highest benefit of squalene-IIV over aqueous IIV in young children and decreasing benefit with progressing age. This trend is similar for seasonal influenza (sub-)types and the 2009 pandemic strain, by both homologous and heterologous titration. The impact of pre-seasonal immunity on vaccine effectiveness, and its implications for age-specific vaccination recommendations, are discussed.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS: Adjuvant; Immunogenicity; Influenza vaccine; Meta-analysis; Pre-seasonal immunity; Squalene

PMID: 31879122 DOI: 10.1016/j.vaccine.2019.12.037

Keywords: Seasonal Influenza; Vaccines.