Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Antiviral Res. 2018 Dec;160:1-9. doi: 10.1016/j.antiviral.2018.10.009. Epub 2018 Oct 11.

Clinical management and viral genomic diversity analysis of a child's influenza A(H1N1)pdm09 infection in the context of a severe combined immunodeficiency.

Author information

1
Hospices Civils de Lyon, Centre National de Référence des virus des infections respiratoires, Laboratoire de Virologie, Institut des Agents Infectieux, Groupement Hospitalier Nord, F-69317, Lyon Cedex 04, France; Univ Lyon, CIRI, Inserm U1111, CNRS UMR5308, ENS, UCBL1, équipe Virpath, Faculté de Médecine Lyon Est, 7-11 Rue Guillaume Paradin, F-69372, Lyon Cedex 08, France.
2
Hospices Civils de Lyon, Centre National de Référence des virus des infections respiratoires, Laboratoire de Virologie, Institut des Agents Infectieux, Groupement Hospitalier Nord, F-69317, Lyon Cedex 04, France.
3
Hospices Civils de Lyon, Institut d'Hématologie et d'Oncologie Pédiatrique, Unité Protégée, 1 Place Joseph Renaut, F-69008, Lyon, France.
4
Hospices Civils de Lyon, Service de Réanimation Pédiatrique, Hôpital Femme Mère Enfant, Groupement Hospitalier Est, 59 Boulevard Pinel, F-69677, Bron, France.
5
Hospices Civils de Lyon, Laboratoire d'Immunologie, Groupement Hospitalier Edouard Herriot, 5 Place d'Arsonval, F-69437, Lyon Cedex 03, France.
6
Hospices Civils de Lyon, Plateforme de séquençage diagnostique, Centre de Biologie et de Pathologie Est, Groupement Hospitalier Est, F-69677, Bron, France.
7
Hospices Civils de Lyon, Centre National de Référence des virus des infections respiratoires, Laboratoire de Virologie, Institut des Agents Infectieux, Groupement Hospitalier Nord, F-69317, Lyon Cedex 04, France; Univ Lyon, CIRI, Inserm U1111, CNRS UMR5308, ENS, UCBL1, équipe Virpath, Faculté de Médecine Lyon Est, 7-11 Rue Guillaume Paradin, F-69372, Lyon Cedex 08, France. Electronic address: vanessa.escuret@chu-lyon.fr.

Abstract

INTRODUCTION:

A child with severe combined immunodeficiency (SCID) had an influenza A(H1N1)pdm09 infection with viral excretion longer than 6 months, during 2013-2014 influenza season, despite cord blood transplantation and antiviral treatments.

METHODS:

Conventional real-time RT-PCR methods were used to estimate viral load and to detect the presence of the common N1 neuraminidase (NA) H275Y substitution responsible for oseltamivir resistance. Next-generation sequencing (NGS) of influenza viruses was performed retrospectively to characterize viral quasispecies in specimens.

RESULTS:

The patient was first treated with oral oseltamivir, leading to detection of low-levels of NA-H275Y substitution. Concomitant cord blood cell transplantation, intravenous administration of zanamivir and immunoglobulins led to an increase in white blood cells and influenza viral load decrease. A viral rebound occurred as soon as the antiviral treatment was discontinued. Eventually, influenza viral load was negated with immune reconstitution. NGS found influenza quasispecies harboring NA-E119A substitution (10.3%). Moreover, NGS showed that viral genomic diversity evolved under antiviral treatment and immune status.

CONCLUSIONS:

Conventional virological techniques were sufficient for influenza infection follow-up but NGS performances allowed characterization of viral variants evolution in this specific case of prolonged influenza virus infection. New and efficient treatments against influenza in immunocompromised patients are needed.

KEYWORDS:

Influenza A(H1N1)pdm09 virus; Intravenous zanamivir; NA-E119A substitution; NA-H275Y substitution; Next-generation sequencing; Oseltamivir resistance

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center