#Antibody levels in a cohort of #pregnant women after the #influenza A #H1N1pdm09 #pandemic: waning and association with self-reported severity and duration of illness (Influenza Other Respir Viruses, abstract)

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

Influenza Other Respir Viruses. 2018 Dec 9. doi: 10.1111/irv.12623. [Epub ahead of print]

Antibody levels in a cohort of pregnant women after the 2009 influenza A(H1N1) pandemic: waning and association with self-reported severity and duration of illness.

Tunheim G1,2, Laake I1, Robertson AH1, Waalen K1, Hungnes O1, Naess LM1, Cox RJ2,3,4, Mjaaland S1,2, Trogstad L1.

Author information: 1 Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, 0213, Oslo, Norway. 2 K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, 0424, Oslo, Norway. 3 The Influenza Centre, Department of Clinical Science, University of Bergen, 5021, Bergen, Norway. 4 Department of Research and Development, Haukeland University Hospital, N5021, Bergen, Norway.




A population-based pregnancy cohort was established in Norway to study potential effects of exposure to the 2009 influenza pandemic or pandemic vaccination during pregnancy.


We studied maternal A(H1N1)pdm09-specific hemagglutination inhibition (HI)-titer levels and waning in women with influenza-like illness (ILI) in pregnancy compared to vaccinated women. Moreover, we studied the association between HI-titers and self-reported severity and duration of ILI.


HI-titers against the pandemic virus were measured in maternal blood samples obtained at birth, 3-9 months after exposure, and linked with information about pregnancy, influenza and vaccination from national registries and a cohort questionnaire.


Among 1821 pregnant women included, 43.7% were unvaccinated and 19.3% of these had ILI. HI-titers were low (geometric mean titer (GMT) 11.3) in the unvaccinated women with ILI. Higher HI-titers (GMT 37.8) were measured in the vaccinated women. Estimated HI-titer waning was similar for vaccinated women and women with ILI. Most ILI episodes were moderate and lasted 3-5 days. Women with ILI reporting specific influenza symptoms such as fever or cough had higher HI-titers than women without these symptoms. Women who reported being “very ill” or illness duration of >5 days, had higher HI-titers than women reporting less severe illness or illness of shorter duration, respectively.


Antibody waning was similar in vaccinated women and women with ILI. More severe ILI or longer duration of illness were associated with higher HI-titers. Most unvaccinated pregnant women with ILI had low HI-titers, probably due to moderate illness and HI-titer waning between exposure and sampling.

This article is protected by copyright. All rights reserved.

KEYWORDS: antibodies; influenza; pandemic H1N1pdm09; pregnancy; vaccination; waning

PMID: 30536590 DOI: 10.1111/irv.12623

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.



#Influenza and #Pregnancy: No Time for #Complacency (Obstet Gynecol., abstract)

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

Obstet Gynecol. 2018 Dec 4. doi: 10.1097/AOG.0000000000003040. [Epub ahead of print]

Influenza and Pregnancy: No Time for Complacency.

Rasmussen SA1, Jamieson DJ.

Author information: 1 University of Florida College of Medicine & College of Public Health and Health Professions, Departments of Pediatrics and Epidemiology, Gainesville, Florida; and Emory University, Department of Gynecology and Obstetrics, Atlanta, Georgia.



The 2009 H1N1 pandemic demonstrated the severe effects of influenza illness on pregnant women. This experience stimulated efforts to improve influenza vaccination coverage among pregnant women and resulted in a substantial increase in coverage from less than 30% before 2009 to more than 50% a few years later. As memories fade of the pandemic year, influenza vaccination coverage has stagnated at around 50%, despite considerable information becoming available on strategies to improve vaccination coverage during pregnancy. The American College of Obstetricians and Gynecologists, through its expert work groups, Committee Opinions, and other outreach efforts, has provided strong support for clinicians to implement these strategies into their practices. Influenza vaccination is the best way to safeguard pregnant women and their infants up to 6 months of age from the adverse outcomes associated with influenza. It is imperative for the obstetric community to redouble its efforts to implement strategies proven to work to improve vaccination coverage and to identify and test new strategies to increase the number of pregnant women and their infants protected from influenza.

PMID: 30531576 DOI: 10.1097/AOG.0000000000003040

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.


The role of #pneumonia and secondary #bacterial infection in #fatal and serious outcomes of #pandemic #influenza A #H1N1pdm09 (BMC Infect Dis., abstract)

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

BMC Infect Dis. 2018 Dec 7;18(1):637. doi: 10.1186/s12879-018-3548-0.

The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09.

MacIntyre CR1, Chughtai AA2, Barnes M3, Ridda I3, Seale H3, Toms R3, Heywood A3.

Author information: 1 Biosecurity Program, The Kirby Institute, UNSW Medicine, University of New South Wales, Sydney, NSW, 2052, Australia. 2 School of Public Health and Community Medicine, Faculty of Medicine, UNSW Medicine, the University of New South Wales, Samuels Building, Room 209, Sydney, NSW, 2052, Australia. journal.health.au@gmail.com. 3 School of Public Health and Community Medicine, Faculty of Medicine, UNSW Medicine, the University of New South Wales, Samuels Building, Room 209, Sydney, NSW, 2052, Australia.




The aim of this study was to estimate the prevalence of pneumonia and secondary bacterial infections during the pandemic of influenza A(H1N1)pdm09.


A systematic review was conducted to identify relevant literature in which clinical outcomes of pandemic influenza A(H1N1)pdm09 infection were described. Published studies (between 01/01/2009 and 05/07/2012) describing cases of fatal or hospitalised A(H1N1)pdm09 and including data on bacterial testing or co-infection.


Seventy five studies met the inclusion criteria. Fatal cases with autopsy specimen testing were reported in 11 studies, in which any co-infection was identified in 23% of cases (Streptococcus pneumoniae 29%). Eleven studies reported bacterial co-infection among hospitalised cases of A(H1N1)2009pdm with confirmed pneumonia, with a mean of 19% positive for bacteria (Streptococcus pneumoniae 54%). Of 16 studies of intensive care unit (ICU) patients, bacterial co-infection identified in a mean of 19% of cases (Streptococcus pneumoniae 26%). The mean prevalence of bacterial co-infection was 12% in studies of hospitalised patients not requiring ICU (Streptococcus pneumoniae 33%) and 16% in studies of paediatric patients hospitalised in general or pediatric intensive care unit (PICU) wards (Streptococcus pneumoniae 16%).


We found that few studies of the 2009 influenza pandemic reported on bacterial complications and testing. Of studies which did report on this, secondary bacterial infection was identified in almost one in four patients, with Streptococcus pneumoniae the most common bacteria identified. Bacterial complications were associated with serious outcomes such as death and admission to intensive care. Prevention and treatment of bacterial secondary infection should be an integral part of pandemic planning, and improved uptake of routine pneumococcal vaccination in adults with an indication may reduce the impact of a pandemic.

KEYWORDS: Bacterial infection; Influenza A(H1N1)pdm09; Pneumonia; Respiratory infections hospitalization

PMID: 30526505 DOI: 10.1186/s12879-018-3548-0

Keywords: Pandemic Influenza; H1N1pdm09; Pneumonia; Streptococcus pneumoniae.


#Vitamin A #Supplementation during #Pregnancy Enhances #H1N1pdm09 #Vaccine Response in #Mothers, but Enhancement of Transplacental #Antibody Transfer May Depend on When Mothers Are Vaccinated during Pregnancy (J Nutr., abstract)

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

J Nutr. 2018 Dec 1;148(12):1968-1975. doi: 10.1093/jn/nxy228.

Vitamin A Supplementation during Pregnancy Enhances Pandemic H1N1 Vaccine Response in Mothers, but Enhancement of Transplacental Antibody Transfer May Depend on When Mothers Are Vaccinated during Pregnancy.

Ahmad SM1, Alam MJ1, Khanam A1, Rashid M1, Islam S1, Kabir Y2, Raqib R1, Steinhoff MC3.

Author information: 1 Infectious Diseases Division, International Center for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka, Bangladesh. 2 Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. 3 Global Health Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.




In the growing embryo, the vitamin A requirement is tightly regulated. Maternal vitamin A deficiency during pregnancy may alter maternal immune function to accommodate the fetus.


Our primary objective was to determine the effect of oral vitamin A supplementation (VAS) during pregnancy and until 6 mo postpartum on pandemic H1N1-vaccine responses in mothers and their infants at 6 mo of age.


In this randomized controlled clinical trial, pregnant women (n = 112) during the second trimester (mean ± SD: 14 ± 1 wk) were assigned to receive either an oral dose of 10,000 IU vitamin A or placebo weekly until 6 mo postpartum. During the third trimester, mothers received a single dose of inactivated pandemic H1N1-influenza vaccine. Hemagglutination-inhibition (HAI) titer was measured in cord, infant, and maternal blood samples. Multivariate regressions with adjustments were used for data analysis.


Seventy-six percent of women had low plasma retinol concentrations (<1.05 μmol/L) in their second trimester. VAS of mothers increased vitamin A concentrations in cord blood by 21.4% and in colostrum by 40.7%. At 6 mo postpartum, women in the vitamin A group had 38.7% higher HAI titers and a higher proportion of HAI titer of ≥1:40 of the cutoff compared with the placebo group. A total of 54.5% of infants had an HAI titer ≥1:40 at 6 mo of age, but there was no difference in HAI titer in infants between groups. Overall, HAI in cord blood did not differ between groups, but in the placebo group, cord blood HAI was negatively associated with maternal “vaccination-to-delivery intervals” (rs = -0.401; P = 0.5), and maternal VAS increased cord blood HAI 6-fold if antenatal immunization was administered ≥10 wk before delivery.


In a community with low vitamin A status, weekly maternal VAS during pregnancy and postpartum increases the breast-milk vitamin A concentration and enhances prenatal H1N1-vaccine responses in mothers, but the benefits of maternal VAS in transplacental antibody transfer may depend on the time of gestation when mothers were vaccinated. This trial was registered at clinicaltrials.gov as NCT00817661.

PMID: 30517724 DOI: 10.1093/jn/nxy228

Keywords: Seasonal Influenza; H1N1pdm09; Vitamin A; Vaccines; Pregnancy.


Duration of #fever and other symptoms after the inhalation of #laninamivir octanoate hydrate in the 2016/17 #Japanese #influenza season; comparison with the 2011/12 to 2015/16 seasons (J Infect Chemother., abstract)

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

J Infect Chemother. 2018 Sep;24(9):718-724. doi: 10.1016/j.jiac.2018.04.013. Epub 2018 Jun 1.

Duration of fever and other symptoms after the inhalation of laninamivir octanoate hydrate in the 2016/17 Japanese influenza season; comparison with the 2011/12 to 2015/16 seasons.

Ikematsu H1, Kawai N2, Iwaki N2, Kashiwagi S2, Ishikawa Y3, Yamaguchi H3, Shiosakai K3.

Author information: 1 Japan Physicians Association, Tokyo, Japan. Electronic address: ikematsu@gray.plala.or.jp. 2 Japan Physicians Association, Tokyo, Japan. 3 Daiichi Sankyo Co., Ltd, Tokyo, Japan.



The duration of fever and symptoms after laninamivir octanoate hydrate (laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

KEYWORDS: Fever; Influenza; Laninamivir; Neuraminidase inhibitor; Symptom

PMID: 29861186 DOI: 10.1016/j.jiac.2018.04.013 [Indexed for MEDLINE]  Free full text

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; Antivirals; Laninamivir; Japan.


Unravelling the Role of O- #glycans in #Influenza A Virus #Infection (Sci Rep., abstract)

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

Article | Open | Published: 06 November 2018

Unravelling the Role of O-glycans in Influenza A Virus Infection

Juliane Mayr, Kam Lau, Jimmy C. C. Lai, Ivan A. Gagarinov, Yun Shi, Sarah McAtamney, Renee W. Y. Chan, John Nicholls, Mark von Itzstein & Thomas Haselhorst

Scientific Reports, volume 8, Article number: 16382 (2018)



The initial stage of host cell infection by influenza A viruses (IAV) is mediated through interaction of the viral haemagglutinin (HA) with cell surface glycans. The binding requirement of IAVs for Galβ(1,4)Glc/ GlcNAc (lactose/lactosamine) glycans with a terminal α(2,6)-linked (human receptors) or α(2,3)-linked (avian receptors) N-acetylneuraminic residue commonly found on N-glycans, is well-established. However the role and significance of sialylated Galβ(1,3)GalNAc (core 1) epitopes that are typical O-glycoforms in influenza virus pathogenesis remains poorly detailed. Here we report a multidisciplinary study using NMR spectroscopy, virus neutralization assays and molecular modelling, into the potential for IAV to engage sialyl-Galβ(1,3)GalNAc O-glycoforms for cell attachment. H5 containing virus like particles (VLPs) derived from an H5N1 avian IAV strain show a significant involvement of the O-glycan-specific GalNAc residue, coordinated by a EQTKLY motif conserved in highly pathogenic avian influenza (HPAI) strains. Notably, human pandemic H1N1 influenza viruses shift the preference from ‘human-like’ α(2,6)-linkages in sialylated Galβ(1,4)Glc/GlcNAc fragments to ‘avian-like’ α(2,3)-linkages in sialylated Galβ(1,3)GalNAc without involvement of the GalNAc residue. Overall, our study suggests that sialylated Galβ(1,3)GalNAc as O-glycan core 1 glycoforms are involved in the influenza A virus life cycle and play a particularly crucial role during infection of HPAI strains.

Keywords: Avian Influenza; H5N1; H1N1; Viral Pathogenesis.


Delayed #oseltamivir plus #sirolimus #treatment attenuates #H1N1 virus-induced severe #lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration (PLoS Pathog., abstract)

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


Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration

Xuehong Jia , Bo Liu , Linlin Bao , Qi Lv, Fengdi Li, Hui Li, Yunqing An, Xulong Zhang , Bin Cao , Chen Wang

Published: November 13, 2018 / DOI: https://doi.org/10.1371/journal.ppat.1007428 / This is an uncorrected proof.



Severe influenza A virus infection causes high mortality and morbidity worldwide due to delayed antiviral treatment and inducing overwhelming immune responses, which contribute to immunopathological lung injury. Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), was effective in improving clinical outcomes in patients with severe H1N1 infection; however, the mechanisms by which it attenuates acute lung injury have not been elucidated. Here, delayed oseltamivir treatment was used to mimic clinical settings on lethal influenza A (H1N1) pdm09 virus (pH1N1) infection mice model. We revealed that delayed oseltamivir plus sirolimus treatment protects mice against lethal pH1N1 infection by attenuating severe lung damage. Mechanistically, the combined treatment reduced viral titer and pH1N1-induced mTOR activation. Subsequently, it suppressed the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated secretion of interleukin (IL)-1β and IL-18. It was noted that decreased NLRP3 inflammasome activation was associated with inhibited nuclear factor (NF)-κB activation, reduced reactive oxygen species production and increased autophagy. Additionally, the combined treatment reduced the expression of other proinflammatory cytokines and chemokines, and decreased inflammatory cell infiltration in lung tissue and bronchioalveolar lavage fluid. Consistently, it inhibited the mTOR-NF-κB-NLRP3 inflammasome-IL-1β axis in a lung epithelial cell line. These results demonstrated that combined treatment with sirolimus and oseltamivir attenuates pH1N1-induced severe lung injury, which is correlated with suppressed mTOR-NLRP3-IL-1β axis and reduced viral titer. Therefore, treatment with sirolimus as an adjuvant along with oseltamivir may be a promising immunomodulatory strategy for managing severe influenza.


Author summary

The severity and lethality of influenza A virus infection are frequently aggravated by virus-induced tissue destruction and overwhelming immune responses. Combined therapy with antiviral medications and immunomodulators, which not only inhibit viral replication, but also reduce the damaging consequences of host immune responses, will be beneficial in the treatment of severe influenza. In the present study, we revealed that pH1N1-induced activation of mTOR promotes lung immunopathological injury, which is correlated with upregulated NF-κB activity and increased reactive oxygen species production. Subsequently, it induces NLRP3 inflammasome activation and the secretion of IL-1β and IL-18. Combined treatment with oseltamivir and the mTOR inhibitor sirolimus (as an adjuvant) not only blocks viral replication, but also suppresses mTOR-NLRP3-IL-1β axis-mediated immune damage, thus protecting mice against lethal pH1N1 infection. Our findings provide the theoretical and experimental basis for the clinical investigation of sirolimus as an adjunct treatment for severe influenza.


Citation: Jia X, Liu B, Bao L, Lv Q, Li F, Li H, et al. (2018) Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration. PLoS Pathog 14(11): e1007428. https://doi.org/10.1371/journal.ppat.1007428

Editor: Paul G. Thomas, St. Jude Children’s Research Hospital, UNITED STATES

Received: April 10, 2018; Accepted: October 22, 2018; Published: November 13, 2018

Copyright: © 2018 Jia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: This work was supported by grants from National Natural Science Foundation of China (81373114) (http://www.nsfc.gov.cn/) and Beijing Municipal Natural Science Foundation (7182013) (http://bjnsf.bjkw.gov.cn/) to XZ, National Science Grant for Distinguished Young Scholars (81425001/H0104) (http://www.nsfc.gov.cn/) and National Key Technology Support Program from Ministry of Science and Technology (2015BAI12B11) (http://www.most.gov.cn/) to BC, and CAMS Innovation Fund for Medical Sciences (2016-I2M-1-014, 2016-12M-006) (www.pumc.edu.cn/) to LB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Influenza A; H1N1pdm09; Antivirals; Oseltamivir; Sirolimus; Animal Models.