Surveillance of antiviral resistance markers in Argentina: detection of E119V neuraminidase mutation in a post-treatment immunocompromised patient.

Andrea Pontoriero,Mara Russo,Elsa Baumeister,Martín Avaro,Ana Zamora,Natalia Periolo,Andrea Czech,Ana Campos,Estefania Benedetti

doi:10.1590/0074-02760160262

Abstract

Although vaccines are the best means of protection against influenza, neuraminidase inhibitors are currently the main antiviral treatment available to control severe influenza cases. One of the most frequent substitutions in the neuraminidase (NA) protein of influenza A(H3N2) viruses during or soon after oseltamivir administration is E119V mutation. We describe the emergence of a mixed viral population with the E119E/V mutation in the NA protein sequence in a post-treatment influenza sample collected from an immunocompromised patient in Argentina. This substitution was identified by a real-time reverse transcriptase polymerase chain reaction (RT-PCR) protocol and was confirmed by direct Sanger sequencing of the original sample. In 2014, out of 1140 influenza samples received at the National Influenza Centre, 888 samples (78%) were A(H3N2) strains, 244 (21.3%) were type B strains, and 8 (0.7%) were A(H1N1)pdm09 strains. Out of 888 A(H3N2) samples, 842 were tested for the E119V substitution by quantitative RT-PCR: 841 A(H3N2) samples had the wild-type E119 genotype and in one sample, a mixture of viral E119/ V119 subpopulations was detected. Influenza virus surveillance and antiviral resistance studies can lead to better decisions in health policies and help in medical treatment planning, especially for severe cases and immunocompromised patients.

Highlights

An immunocompromised host is a patient who does not have the ability to respond normally to an infection due to weakened immune system
We describe the emergence of the E119V substitution in the NA protein of an influenza A(H3N2) isolate detected in a clinical specimen collected from an immunocompromised patient after oseltamivir treatment in Argentina during 2014 epidemic season
In 2014, the National Influenza and Respiratory Virus Surveillance Network (NIRN) analysed a total of 51,744 samples for the detection of respiratory virus isolates that came from paediatric and adult inpatients and outpatients with acute lower and upper respiratory tract infections

Summary

Introduction

An immunocompromised host is a patient who does not have the ability to respond normally to an infection due to weakened immune system This inability to fight infection makes these patients susceptible to bacterial, fungal, and viral infections, such as influenza (Eshaghi et al 2014). Antiviral prophylaxis and therapy are important in these patients because the influenza vaccine is often poorly immunogenic and unlikely to be fully protective (Yousuf et al 1997). These patients are at risk of developing antiviral resistance and subsequent complications. Mixed viral populations that contained sensitive and resistant viruses in different proportions have been detected in intra-treatment samples collected from paediatric patients (Valinotto et al 2010). We describe the emergence of the E119V substitution in the NA protein of an influenza A(H3N2) isolate detected in a clinical specimen collected from an immunocompromised patient after oseltamivir treatment in Argentina during 2014 epidemic season

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