#Paradoxical clade- and age-specific #vaccine #effectiveness during the 2018/19 #influenza A #H3N2 #epidemic in #Canada: potential imprint-regulated effect of vaccine (I-REV) (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV)

Danuta M Skowronski 1,2, Suzana Sabaiduc 1, Siobhan Leir 1, Caren Rose 1,2, Macy Zou 1, Michelle Murti 3,4, James A Dickinson 5, Romy Olsha 3, Jonathan B Gubbay 3,4, Matthew A Croxen 6,7, Hugues Charest 8, Nathalie Bastien 9, Yan Li 9, Agatha Jassem 1,2, Mel Krajden 1,2, Gaston De Serres 8,10,11

Affiliations: 1 British Columbia Centre for Disease Control, Vancouver, Canada; 2 University of British Columbia, Vancouver, Canada; 3 Public Health Ontario, Toronto, Canada; 4 University of Toronto, Toronto, Canada; 5 University of Calgary, Calgary, Canada; 6 Alberta Precision Laboratories, Edmonton, Alberta; 7 University of Alberta, Edmonton, Canada; 8 Institut National de Santé Publique du Québec, Québec, Canada; 9 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada; 10 Laval University, Quebec, Canada11 Centre Hospitalier Universitaire de Québec, Québec, Canada

Correspondence:  Danuta M Skowronski

Citation style for this article: Skowronski Danuta M, Sabaiduc Suzana, Leir Siobhan, Rose Caren, Zou Macy, Murti Michelle, Dickinson James A, Olsha Romy, Gubbay Jonathan B, Croxen Matthew A, Charest Hugues, Bastien Nathalie, Li Yan, Jassem Agatha, Krajden Mel, De Serres Gaston. Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV). Euro Surveill. 2019;24(46):pii=1900585. https://doi.org/10.2807/1560-7917.ES.2019.24.46.1900585

Received: 19 Sep 2019;   Accepted: 04 Nov 2019




The Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic.


To explain a paradoxical signal of increased clade 3C.3a risk among 35–54-year-old vaccinees, we hypothesise childhood immunological imprinting and a cohort effect following the 1968 influenza A(H3N2) pandemic.


We assessed VE by test-negative design for influenza A(H3N2) overall and for co-circulating clades 3C.2a1b and 3C.3a. VE variation by age in 2018/19 was compared with amino acid variation in the haemagglutinin glycoprotein by year since 1968.


Influenza A(H3N2) VE was 17% (95% CI: −13 to 39) overall: 27% (95% CI: −7 to 50) for 3C.2a1b and −32% (95% CI: −119 to 21) for 3C.3a. Among 20–64-year-olds, VE was −7% (95% CI: −56 to 26): 6% (95% CI: −49 to 41) for 3C.2a1b and −96% (95% CI: −277 to −2) for 3C.3a. Clade 3C.3a VE showed a pronounced negative dip among 35–54-year-olds in whom the odds of medically attended illness were > 4-fold increased for vaccinated vs unvaccinated participants (p < 0.005). This age group was primed in childhood to influenza A(H3N2) viruses that for two decades following the 1968 pandemic bore a serine at haemagglutinin position 159, in common with contemporary 3C.3a viruses but mismatched to 3C.2a vaccine strains instead bearing tyrosine.


Imprinting by the first childhood influenza infection is known to confer long-lasting immunity focused toward priming epitopes. Our findings suggest vaccine mismatch may negatively interact with imprinted immunity. The immunological mechanisms for imprint-regulated effect of vaccine (I-REV) warrant investigation.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Seasonal Influenza; Vaccines; H3N2; Origin Antigenic Sin; Canada.


#Outcomes and #Adverse Effects With #Peramivir for the #Treatment of #Influenza #H1N1 in Critically Ill #Pediatric Patients (J Pediatr Pharmacol Ther., abstract)

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

J Pediatr Pharmacol Ther. 2019 Nov-Dec;24(6):497-503. doi: 10.5863/1551-6776-24.6.497.

Outcomes and Adverse Effects With Peramivir for the Treatment of Influenza H1N1 in Critically Ill Pediatric Patients.

Witcher R, Tracy J, Santos L, Chopra A.




Influenza is an environmental pathogen and infection presents as a range from asymptomatic to fulminant illness. Though treatment is supportive, antiviral agents have a role in the management of infection. Pediatric use of peramivir is largely based on reports and extrapolations of pharmacokinetic data. We seek to describe efficacy and safety of peramivir in critically ill pediatric patients.


This is a retrospective, institutional review board-approved chart review of all patients under 21 years of age, admitted to the PICU, and treated with peramivir for influenza H1N1 infection between January 1, 2016, and March 31, 2016, at a single-center, 12-bed PICU. The primary outcome was time to sustained resolution of fever; secondary outcomes included dose, duration, and adverse effects of peramivir therapy.


Seven patients were included with median age of 3.7 years. Median time to sustained resolution of fever was 49.3 hours, median duration of mechanical ventilation was 14.2 days, median ICU LOS was 18.7 days, and hospital LOS was 24.7 days. No patients suffered mortality. Three patients experienced leukopenia, one of which experienced a concurrent neutropenia. Three patients experienced hyperglycemia, 2 experienced hypertension, 1 experienced increased aspartate aminotransferase and increased alanine aminotransferase, and 1 experienced diarrhea. All adverse events assessed were classified as possible using published adverse event causality assessments.


Peramivir has been shown to be an effective therapy for the treatment of influenza H1N1 in critically ill pediatric patients. In our experience with 7 pediatric patients, peramivir was well tolerated at typical durations of therapy; however, increased vigilance is warranted during prolonged courses or in patients with reasons for altered pharmacokinetics and pharmacodynamics.

Copyright Published by the Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2019.

KEYWORDS: adverse drug events; critical care; influenza; pediatric; safety

PMID: 31719811 PMCID: PMC6836703 DOI: 10.5863/1551-6776-24.6.497

Keywords: Seasonal Influenza; H1N1; Antivirals; Drugs safety; Peramivir; Pediatrics.


Antecedent #infections in #GBS: a single-center, prospective study (Ann Clin Transl Neurol., abstract)

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

Ann Clin Transl Neurol. 2019 Nov 12. doi: 10.1002/acn3.50946. [Epub ahead of print]

Antecedent infections in Guillain-Barré syndrome: a single-center, prospective study.

Hao Y1, Wang W1, Jacobs BC2, Qiao B1, Chen M3, Liu D1, Feng X1, Wang Y1,4.

Author information: 1 Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China. 2 Department of Neurology and Immunology, Erasmus University Medical Centre, Rotterdam, The Netherlands. 3 Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, Hunan Province, China. 4 Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China.




To investigate the spectrum of antecedent infections in Chinese patients with Guillain-Barré syndrome (GBS) and analyze the infections-related clinical phenotypes locally.


A prospective case-control study of 150 patients diagnosed with GBS and age- and sex-matched neurological and healthy controls was performed to investigate recent infections of 14 pathogens serologically and collect the clinical data during a follow-up of 12 months.


In total, 53% of patients with GBS had a positive serology for recent infection, including Campylobacter jejuni (27%), influenza A (17%) and B (16%), hepatitis A virus (5%), dengue virus (3%), cytomegalovirus (3%), Epstein-Barr virus (3%), Mycoplasma pneumoniae (2%), herpes simplex virus (2%), varicella-zoster virus (1%), and rubella virus (1%). Serology for infections of hepatitis E virus, Haemophilus influenzae, and Zika virus was negative. There was a higher frequency of C. jejuni, influenza A, influenza B, and hepatitis A virus infections in GBS patients than both the neurological and healthy controls. C. jejuni infection was more frequent in younger GBS patients and was associated with antibodies against GM1, GalNAc-GD1a, and GM1:galactocerebroside complex. Influenza B infection was associated with a pure motor form of GBS.


C. jejuni, influenza A, influenza B, and hepatitis A virus serve as the most common cause of antecedent infections in GBS locally. Influenza B-related GBS may represent a pure motor phenotype. Differences in the infectious spectrum worldwide may contribute to the geographical clinical heterogeneity of GBS.

© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

PMID: 31714025 DOI: 10.1002/acn3.50946

Keywords: GBS; Neurology; Hepatitis A; Seasonal Influenza.


#Influenza A #H1N1pdm09 Virus #Infection in a Captive Giant #Panda, #HK (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 12—December 2019 / Dispatch

Influenza A(H1N1)pdm09 Virus Infection in a Captive Giant Panda, Hong Kong

Paolo Martelli1, Jade L.L. Teng1, Foo-Khong Lee, Kai-Yan Yeong, Jordan Y.H. Fong, Suk-Wai Hui, Kwok-Hung Chan, Susanna K.P. Lau, and Patrick C.Y. Woo

Author affiliations: Ocean Park Corporation, Hong Kong, China (P. Martelli, F.-K. Lee, S.-W. Hui); The University of Hong Kong, Hong Kong (J.L.L. Teng, K.-Y. Yeong, J.Y.H. Fong, K.-H. Chan, S.K.P. Lau, P.C.Y. Woo); State Key Laboratory of Emerging Infectious Diseases at the University of Hong Kong, Hong Kong (J.L.L. Teng, K.-H. Chan, S.K.P. Lau, P.C.Y. Woo); Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases at the University of Hong Kong, Hong Kong (S.K.P. Lau, P.C.Y. Woo)



We report influenza A(H1N1)pdm09 virus infection in a captive giant panda in Hong Kong. The viral load peaked on day 1 and became undetectable on day 5, and an antibody response developed. Genome analysis showed 99.3%–99.9% nucleotide identity between the virus and influenza A(H1N1)pdm09 virus circulating in Hong Kong.

Keywords: Seasonal Influenza; H1N1pdm09; Giant Panda; HK PRC SAR.


#Assessment of #Effectiveness of Seasonal #Influenza #Vaccination During #Pregnancy in Preventing Influenza Infection in #Infants in #England, 2013–2014 and 2014–2015 (J Infect Dis., abstract)

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

Assessment of Effectiveness of Seasonal Influenza Vaccination During Pregnancy in Preventing Influenza Infection in Infants in England, 2013–2014 and 2014–2015

Jemma L Walker, Hongxin Zhao, Gavin Dabrera, Nick Andrews, Sarah L Thomas, Camille Tsang, Joanna Ellis, Matthew Donati, Richard G Pebody

The Journal of Infectious Diseases, jiz310, https://doi.org/10.1093/infdis/jiz310

Published: 09 November 2019



Maternal influenza vaccination is increasingly recognized to protect infants from influenza infection in their first 6 months. We used the screening method to estimate vaccine effectiveness (VE) against laboratory-confirmed influenza in infants in England, using newly available uptake data from the Clinical Practice Research Datalink pregnancy register, matched on week of birth and region and adjusted for ethnicity. We found VE of 66% (95% confidence interval [CI], 18%–84%) in the 2013–2014 season and 50% (95% CI, 11%–72%) in 2014–2015, with similar VE against influenza-related hospitalization. VE against the dominant circulating influenza strain was higher, at 78% (95% CI, 16%–94%) against H1N1 in 2013–2014, and 60% (95% CI, 16%–81%) against H3N2 in 2014–2015.

influenza, vaccine effectiveness, pregnancy, infants, electronic health records

Issue Section: Brief Report

Keywords: Seasonal Influenza; Pregnancy; Vaccines; Pediatrics; England.


#Effectiveness of four types of #neuraminidase #inhibitors approved in #Japan for the #treatment of #influenza (PLoS One, abstract)

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

PLoS One. 2019 Nov 7;14(11):e0224683. doi: 10.1371/journal.pone.0224683. eCollection 2019.

Effectiveness of four types of neuraminidase inhibitors approved in Japan for the treatment of influenza.

Mawatari M1, Saito R1, Hibino A1, Kondo H1, Yagami R1, Odagiri T1,2, Tanabe I1, Shobugawa Y1; Japanese Influenza Collaborative Study Group.

Author information: 1 Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan. 2 Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, Iwate, Japan.




Neuraminidase inhibitors (NAIs) effectively treat influenza. The clinical effectiveness of four NAIs (oseltamivir, zanamivir, laninamivir, and peramivir) was evaluated against influenza A/H1N1pdm09, A/H3N2, and B viruses. Additionally, fever duration in patients infected with oseltamivir-resistant influenza A/H1N1pdm09 with the H275Y mutation was evaluated.


Patients aged <20 years who visited outpatient clinics in Japan with influenza-like illnesses were enrolled during 4 influenza seasons from 2012/2013 to 2015/2016. After obtaining informed consent, patients who tested positive for influenza with rapid tests received one of the four NAIs. Patients recorded their body temperature daily for 8 days from the first visit. The influenza strain was identified using real-time polymerase chain reaction. Univariate and multivariable analyses were used to evaluate factors influencing fever duration. In children aged ≤5 years treated with oseltamivir, fever duration in oseltamivir-resistant A/H1N1pdm09-infected patients was compared to that in oseltamivir-sensitive A/H1N1pdm09-infected patients.


Of the 1,368 patients analyzed, 297 (21.7%), 683 (49.9%), and 388 (28.4%) were infected with influenza A/H1N1pdm09, A/H3N2, and B, respectively. In multivariable analysis factors associated with significantly prolonged fever duration included: treatment with laninamivir (hazard ratio [HR]: 0.78, p = 0.006, compared to oseltamivir), influenza B (HR: 0.58, p<0.001, compared to influenza A/H1N1pdm09), and a higher body temperature at the clinic visit (HR: 0.87 per degree Celsius, p<0.001). Increasing age was associated with a significantly shorter duration of fever (HR: 1.31 for 6-9 years old, p<0.001; and HR: 1.65 for 10-19 years old, p<0.001, respectively, compared to 0-5 years old). Following treatment with oseltamivir, fever duration was significantly longer for oseltamivir-resistant A/H1N1pdm09-infected patients (n = 5) than for oseltamivir-sensitive A/H1N1pdm09 infected patients (n = 111) (mean, 89 versus 40 hours, p<0.001).


Our results revealed characteristic information on the effectiveness of the four NAIs and also on oseltamivir-resistant viruses that may affect patients’ clinical care.

PMID: 31697721 DOI: 10.1371/journal.pone.0224683

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir; Laninamivir; Japan.


Acute #Macular #Neuroretinopathy Associated with Acute #Influenza Virus #Infection (Ocul Immunol Inflamm., abstract)

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

Ocul Immunol Inflamm. 2019 Nov 7:1-7. doi: 10.1080/09273948.2019.1681470. [Epub ahead of print]

Acute Macular Neuroretinopathy Associated with Acute Influenza Virus Infection.

Ashfaq I1, Vrahimi M1, Waugh S2, Soomro T1, Grinton ME1, Browning AC1.

Author information: 1 Ophthalmology Department, Newcastle Eye Centre, Newcastle upon Tyne, UK. 2 Virology Department, Freeman Hospital, Newcastle upon Tyne, UK.




To describe a prospective case series of patients with acute macular neuroretinopathy (AMN) associated with acute influenza virus infection.


Patients who presented with acute macular neuroretinopathy associated with confirmed influenza virus infection were subject to a detailed clinical history, HLA typing and longitudinal ophthalmological and imaging examinations.


Four female patients aged 18 to 32 years were studied. They reported the onset of ocular symptoms between 2 and 5 days after the development of flu like symptoms. Three patients had confirmed acute influenza B infection, while the fourth had influenza A. OCT angiography only demonstrated abnormal choriocapillaris perfusion in 1 patient and early oral Oseltamivir treatment appeared not to affect the ophthalmic outcome in one patient.


This is the first report of AMN associated with virologically confirmed acute influenza virus infection. Variation in HLA alleles do not appear to predispose patients to influenza associated AMN.

KEYWORDS: AMN; HLA typing; Influenza; OCT

PMID: 31697568 DOI: 10.1080/09273948.2019.1681470

Keywords: Seasonal Influenza; Ophthalmology.