#Oseltamivir #resistance in #severe #influenza A #H1N1pdm09 #pneumonia and #ARDS: a #French multicenter observational cohort study (Clin Infect Dis., abstract)

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

Clin Infect Dis. 2019 Sep 20. pii: ciz904. doi: 10.1093/cid/ciz904. [Epub ahead of print]

Oseltamivir resistance in severe influenza A(H1N1)pdm09 pneumonia and acute respiratory distress syndrome: a French multicenter observational cohort study.

Behillil S1, May F2,3, Fourati S4, Luyt CE5, Chicheportiche T5, Sonneville R6, Tandjaoui-Lambiotte Y7, Roux D8, Guérin L9, Mayaux J10, Maury E11, Ferré A12, Georger JF13, Voiriot G14, Enouf V1, van der Werf S1, Dessap AM2,3, de Prost N2,3.

Author information: 1 Unité de Génétique Moléculaire des Virus à ARN et Centre National de Référence des Virus des Infections Respiratoires (dont la grippe), Institut Pasteur, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 2 Service de Réanimation Médicale, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France. 3 Groupe de Recherche Clinique CARMAS, Université Paris-Est Créteil, IMRB, Créteil,  France. 4 Département de Microbiologie, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France. 5 Service de Médecine Intensive Réanimation, Hôpital de La Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 6 Service de Médecine Intensive Réanimation, Hôpital Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France. 7 Service de Réanimation médico-chirurgicale, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, France. 8 Service de réanimation médico-chirurgicale, Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris, Colombes,  France; IAME, Université Paris Diderot, Paris, France. 9 Service de réanimation médicale, Hôpital Bicètre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicètre, France. 10 Service de Réanimation Médicale et Pneumologie, Hôpital de La Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 11 Service de Réanimation Médicale, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France. 12 Service de Réanimation, Centre hospitalier de Versailles, Le Chesnay, France. 13 Service de Réanimation, Centre hospitalier Intercommunal de Villeneuve Saint-Georges, Villeneuve Saint-Georges, France. 14 Service de Réanimation Médicale, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France.

 

Abstract

In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day-28 mortality than others (80% vs 12%; p=0.011).

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

KEYWORDS: Influenza A Virus, H1N1 Subtype; Oseltamivir; Pneumonia, Viral; Respiratory Distress Syndrome, Adult

PMID: 31538643 DOI: 10.1093/cid/ciz904

Keywords: Seasonal Influenza; H1N1pdm09; Antivirals; Drugs Resistance; Oseltamivir; Pneumonia; ARDS; France.

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Replicative #fitness of seasonal #influenza A viruses with decreased susceptibility to #baloxavir (J Infect Dis., abstract)

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

Replicative fitness of seasonal influenza A viruses with decreased susceptibility to baloxavir

Anton Chesnokov, Mira C Patel, Vasiliy P Mishin, Juan A De La Cruz, Lori Lollis, Ha T Nguyen, Vivien Dugan, David E Wentworth, Larisa V Gubareva

The Journal of Infectious Diseases, jiz472, https://doi.org/10.1093/infdis/jiz472

Published: 21 September 2019

 

Abstract

Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold), but also on in vitro replicative fitness. While I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir resistant viruses needed for informed risk assessment.

Cap-dependent endonuclease inhibitor, replicative fitness, polymerase acidic protein, influenza, drug resistance, ferret, baloxavir acid, antiviral

Issue Section: Brief Report

This content is only available as a PDF.

Author notes

These authors contributed equally to this article and share first authorship

Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Influenza A; Antivirals; Drugs Resistance; Baloxavir.

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#Effect of #measles #vaccination in #infants younger than 9 months on the immune response to subsequent measles vaccine doses: a systematic review and meta-analysis (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Effect of measles vaccination in infants younger than 9 months on the immune response to subsequent measles vaccine doses: a systematic review and meta-analysis

Laura M Nic Lochlainn, PhD, Brechje de Gier, PhD, Nicoline van der Maas, PhD, Rob van Binnendijk, PhD, Peter M Strebel, MBChB, Tracey Goodman, MA, Hester E de Melker, PhD, Prof William J Moss, MD, Susan J M Hahné, PhD

Open Access / Published: September 20, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30396-2

 

Summary

Background

Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related morbidity and mortality. However, there is concern that early vaccination might blunt the immune response to subsequent measles vaccine doses. We systematically reviewed the available evidence on the effect of MCV1 administration to infants younger than 9 months on their immune responses to subsequent MCV doses.

Methods

For this systematic review and meta-analysis, we searched for randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We included studies reporting data on strength or duration of humoral and cellular immune responses, and on vaccine efficacy or vaccine effectiveness after two-dose or three-dose MCV schedules. Our outcome measures were proportion of seropositive infants, geometric mean titre, vaccine efficacy, vaccine effectiveness, antibody avidity index, and T-cell stimulation index. We used random-effects meta-analysis to derive pooled estimates of the outcomes, where appropriate. We assessed the methodological quality of included studies using Grading of Recommendation Assessment, Development and Evaluation (GRADE) guidelines.

Findings

Our search retrieved 1156 records and 85 were excluded due to duplication. 1071 records were screened for eligibility, of which 351 were eligible for full-text screening and 21 were eligible for inclusion in the review. From 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI 96–99; I2=79·8%, p<0·0001), which was not significantly different from seropositivity after a two-dose MCV schedule starting later (p=0·087). Only one of four studies found geometric mean titres after MCV2 administration to be significantly lower when MCV1 was administered before 9 months of age than at 9 months of age or later. There was insufficient evidence to determine an effect of age at MCV1 administration on antibody avidity. The pooled vaccine effectiveness estimate derived from two studies of a two-dose MCV schedule with MCV1 vaccination before 9 months of age was 95% (95% CI 89–100; I2=12·6%, p=0·29). Seven studies reporting on measles virus-specific cellular immune responses found that T-cell responses and T-cell memory were sustained, irrespective of the age of MCV1 administration. Overall, the quality of evidence was moderate to very low.

Interpretation

Our findings suggest that administering MCV1 to infants younger than 9 months followed by additional MCV doses results in high seropositivity, vaccine effectiveness, and T-cell responses, which are independent of the age at MCV1, supporting the vaccination of very young infants in high-risk settings. However, we also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older. The clinical and public-health relevance of this immunity blunting effect are uncertain.

Funding

WHO.

Keywords: Measles; Vaccines; Pediatrics.

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Immunogenicity, #effectiveness, and #safety of #measles #vaccination in #infants younger than 9 months: a systematic review and meta-analysis (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis

Laura M Nic Lochlainn, PhD, Brechje de Gier, PhD, Nicoline van der Maas, PhD, Peter M Strebel, MBChB, Tracey Goodman, MA, Rob S van Binnendijk, PhD, Hester E de Melker, PhD, Susan J M Hahné, PhD

Open Access / Published: September 20, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30395-0

 

Summary

Background

Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months.

Methods

For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, Proquest, Global Health, the WHO library database, and the WHO Institutional Repository for Information Sharing database, and consulted experts. We included randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We assessed: proportion of infants seroconverted, geometric mean antibody titre, avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness, and safety. We used random-effects models to derive pooled estimates of the endpoints, where appropriate. We assessed methodological quality using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines.

Findings

Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29–71) for those vaccinated with MCV1 at 4 months of age to 85% (69–97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4–8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0·46 (95% CI 0·33–0·66; I2=99·9%, p<0·0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0·0016) or 12 months of age (p<0·001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74–98) in infants vaccinated with MCV1 at 4·5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9–80; I2=84·9%, p<0·0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI −44 to 83; I2=92·3%, p<0·0001), and for those aged 9 months and older at vaccination it was 83% (76–88; I2=93·8%, p<0·0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low.

Interpretation

MCV1 administered to infants younger than 9 months induces a good immune response, whereby the proportion of infants seroconverted increases with increased age at vaccination. A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity.

Funding

WHO.

Keywords: Measles; Vaccines; Pediatrics.

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Experimental #H1N1pdm09 #infection in #pigs mimics #human seasonal #influenza #infections (PLoS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Experimental H1N1pdm09 infection in pigs mimics human seasonal influenza infections

Theresa Schwaiger, Julia Sehl, Claudia Karte, Alexander Schäfer, Jane Hühr, Thomas C. Mettenleiter, Charlotte Schröder, Bernd Köllner, Reiner Ulrich, Ulrike Blohm

Published: September 20, 2019 / DOI: https://doi.org/10.1371/journal.pone.0222943

 

Abstract

Pigs are anatomically, genetically and physiologically comparable to humans and represent a natural host for influenza A virus (IAV) infections. Thus, pigs may represent a relevant biomedical model for human IAV infections. We set out to investigate the systemic as well as the local immune response in pigs upon two subsequent intranasal infections with IAV H1N1pdm09. We detected decreasing numbers of peripheral blood lymphocytes after the first infection. The simultaneous increase in the frequencies of proliferating cells correlated with an increase in infiltrating leukocytes in the lung. Enhanced perforin expression in αβ and γδ T cells in the respiratory tract indicated a cytotoxic T cell response restricted to the route of virus entry such as the nose, the lung and the bronchoalveolar lavage. Simultaneously, increasing frequencies of CD8αα expressing αβ T cells were observed rapidly after the first infection, which may have inhibited uncontrolled inflammation in the respiratory tract. Taking together, the results of this study demonstrate that experimental IAV infection in pigs mimics major characteristics of human seasonal IAV infections.

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Citation: Schwaiger T, Sehl J, Karte C, Schäfer A, Hühr J, Mettenleiter TC, et al. (2019) Experimental H1N1pdm09 infection in pigs mimics human seasonal influenza infections. PLoS ONE 14(9): e0222943. https://doi.org/10.1371/journal.pone.0222943

Editor: Balaji Manicassamy, University of Iowa, UNITED STATES

Received: May 28, 2019; Accepted: September 10, 2019; Published: September 20, 2019

Copyright: © 2019 Schwaiger 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 manuscript and its Supporting Information files.

Funding: This study was funded by Federal Excellence Initiative of Mecklenburg Western Pomerania and European Social Fund (ESF) Grant KoInfekt (ESF_14-BM-A55-00xx_16) to TCM.

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

Keywords: Seasonal Influenza; H1N1pdm09; Human; Pigs; Animal models.

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#Molecular confirmation and #phylogeny of #Lassa fever virus in #Benin Republic 2014-2016 (Afr J Lab Med., abstract)

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

Afr J Lab Med. 2019 Aug 22;8(1):803. doi: 10.4102/ajlm.v8i1.803. eCollection 2019.

Molecular confirmation and phylogeny of Lassa fever virus in Benin Republic 2014-2016.

Salu OB1,2, James AB2,3, Bankolé HS4,5, Agbla JM5, Da Silva M5, Gbaguidi F5,6, Loko CF7, Omilabu SA1,2.

Author information: 1 Department of Medical Microbiology and Parasitology, College of Medicine, University of Lagos, Lagos, Nigeria. 2 Centre for Human and Zoonotic Virology, Central Research Laboratory, College of Medicine, University of Lagos, Lagos, Nigeria. 3 Department of Biochemistry, College of Medicine, University of Lagos, Lagos, Nigeria. 4 Department of Applied Microbiology and Pharmacology of Natural Sciences, University of Abomey-Calavi, Abomey-Calavi, Benin, Benin. 5 National Laboratory of Public Health, Ministry of Health, Benin, Benin. 6 Department of Pharmacognosy and Pharmaceutical Organic Chemistry, University of Abomey-Calavi, Abomey-Calavi, Benin. 7 De la Pharmacie, du Medicament et des Explorations Diagnostiques, Ministére de la Santé, Cotonou, Benin.

 

Abstract

BACKGROUND:

The changing epidemiology of the Lassa virus from endemic areas to other parts of West Africa has been reported. However, there have been no documented Lassa fever transmission chains in the Benin Republic. Two outbreaks of Lassa fever (November 2014 and January 2016) in the Benin Republic were characterised by a high number of deaths (more than 50%) among 27 confirmed and other unconfirmed cases.

OBJECTIVES:

We report the detection, confirmation and relatedness of the Lassa virus strains from the Benin Republic with other isolates within the West African Sub-region.

METHODS:

A total of 70 blood samples (16 from 2014 and 54 from 2016) from suspected cases with signs and symptoms suggestive of viral haemorrhagic fever were received for molecular analysis at the Centre for Human and Zoonotic Virology, College of Medicine, University of Lagos and the Lagos University Teaching Hospital. With the detection of the Lassa virus RNA by reverse transcriptase polymerase chain reaction, sequencing and phylogenetic analyses were performed using the Sanger dideoxy sequencing technology platform and the MEGA6 software.

RESULTS:

S segments of the Lassa virus RNA genome were detected in 5 (7.1%) of the 70 samples analysed. Sequencing and a phylogenetic tree construction confirmed that the strain of Lassa virus had close relationships with strains previously isolated from Nigeria.

CONCLUSION:

We confirmed the presence of the Lassa virus in the Benin Republic, with 2 strains having molecular epidemiological links with Lineage I and II strains from Nigeria. To reduce the likelihood of outbreaks, there is a need for heightened awareness and strengthened surveillance systems about Lassa fever, particularly in the sub-region.

KEYWORDS: Benin Republic; Lassa virus; West Africa; phylogeny; surveillance

PMID: 31534915 PMCID: PMC6739551 DOI: 10.4102/ajlm.v8i1.803

Keywords: Lassa fever; Benin; Nigeria.

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A novel #reassortant #influenza A (#H1N1) virus #infection in #swine in #Shandong Province, eastern #China (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Sep 19. doi: 10.1111/tbed.13360. [Epub ahead of print]

A novel reassortant influenza A (H1N1) virus infection in swine in Shandong Province, eastern China.

Yu Z1,2,3, Cheng K4, He H5, Wu J1,2,3.

Author information: 1 Poultry Institute, Shandong Academy of Agricultural Sciences, Jinan, 250023, China. 2 Shandong Provincial Key Laboratory of Poultry Diseases Diagnosis and Immunology. 3 Poultry Breeding Engineering Technology Center of Shandong Province. 4 Dairy Cattle Research Center, Shandong Academy of Agricultural Sciences, Jinan, 250132, China. 5 College of Life Sciences, Shandong Normal University, Jinan, 250014, China.

 

Abstract

Influenza A (H1N1) viruses are distributed worldwide and pose a threat to public health. Swine, as a natural host and mixing vessel of influenza A (H1N1) virus, play a critical role in the transmission of this virus to humans. Furthermore, swine influenza A (H1N1) viruses have provided all eight genes or some genes to the genomes of influenza strains that historically have caused human pandemics. Hence, persistent surveillance of influenza A (H1N1) virus in swine herds could contribute to the prevention and control of this virus. Here, we report a novel reassortant influenza A (H1N1) virus generated by reassortment between 2009 pandemic H1N1 viruses and swine viruses. We also found that this virus is prevalent in swine herds in Shandong Province, eastern China. Our findings suggest that surveillance of the emergence of the novel reassortant influenza A (H1N1) virus in swine is imperative.

© 2019 Blackwell Verlag GmbH.

KEYWORDS: H1N1; human; influenza; reassortant; swine

PMID: 31535780 DOI: 10.1111/tbed.13360

Keywords: Seasonal Influenza; Swine Influenza; H1N1; H1N1pdm09; Pigs; Reassortant strain; Shandong; China.

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