Guidance for clinical and public health laboratories testing for influenza virus antiviral drug susceptibility in Europe

Pozo, Francisco; Lina, Bruno; Rebelo-de-Andrade, Helena; Enouf, Vincent; Kossyvakis, Athanasios; Broberg, Eeva; Daniels, Rod S.; Lackenby, Angie; Meijer, Adam

doi:10.1016/j.jcv.2013.01.009

Cited by 28 publications

(23 citation statements)

References 32 publications

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“…Besides H275Y and R292K, no other substitution associated with resistance was detected in the NA. This suggests that as opposed to observations in immunocompromised, these 2 positions are almost the exclusive “hot spots” for changes associated with antiviral resistance in the context of oseltamivir pressure in immunocompetent patients 14, 20…”

Section: Discussionmentioning

confidence: 78%

“…Patients had throat or nasal swabs collected on days 1, 3 (self‐swab), 6 and 10 for real‐time reverse transcription PCR (RT‐PCR) analyses of influenza type, subtype and susceptibility to NAI. NAI susceptibility was determined according to the IC 50 values performed on the viruses by a chemiluminescent assay (NA‐Star), and the measure of the fold increase observed as compared to IC 50 values of susceptible strains, according to the common procedure 14, 15. Resistant viruses were either with a reduced inhibition (RI) or a highly reduced inhibition (HRI), depending on the fold increase as per the WHO GISRS guidelines.…”

Section: Methodsmentioning

confidence: 99%

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Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study

Lina

Boucher

Osterhaus

et al. 2018

Influenza Resp Viruses

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Background and objectivesThe Influenza Resistance Information Study (IRIS) was initiated in 2008 to study the emergence of neuraminidase inhibitor (NAI) resistance and the clinical course of influenza in immunocompetent treated and untreated patients.MethodsPatients had throat/nose swabs collected on days 1, 3, 6 and 10 for analyses of influenza type, subtype and virus susceptibility to NAIs. RT‐PCR‐positive samples were cultured and tested for NAI resistance by specific RT‐PCR and phenotypic testing. Scores for influenza symptoms were recorded on diary cards (Days 1‐10). This study focuses on influenza A‐infected cases only.ResultsAmong 3230 RT‐PCR‐positive patients, 2316 had influenza A of whom 1216 received oseltamivir monotherapy within 2 days of symptom onset (9 seasonal H1N1; 662 H3N2; 545 H1N1pdm2009). Except for 9 patients with naturally resistant seasonal H1N1 (2008/9), no resistance was detected in Day 1 samples. Emergence of resistance (post‐Day 1) was detected in 43/1207 (3.56%) oseltamivir‐treated influenza A‐infected patients, with a higher frequency in 1‐ to 5‐year‐olds (11.8%) vs >5‐year‐olds (1.4%). All N1‐ and N2‐resistant viruses had H275Y (n = 27) or R292K (n = 16) substitutions, respectively. For 43 patients, virus clearance was significantly delayed vs treated patients with susceptible viruses (8.1 vs 10.9 days; P < .0001), and 11 (23.2%) remained RT‐PCR positive for influenza at Day 10. However, their symptoms resolved by Day 6 or earlier.ConclusionsOseltamivir resistance was only detected during antiviral treatment, with the highest incidence occurring among 1‐ to 5‐year‐olds. Resistance delayed viral clearance, but had no impact on symptom resolution.

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Section: Discussionmentioning

confidence: 78%

Section: Methodsmentioning

confidence: 99%

Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study

Lina

Boucher

Osterhaus

et al. 2018

Influenza Resp Viruses

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“…To gauge the severity of this problem for the influenza B viruses generated here, we determined the amount of NAI-resistant virus needed to overcome concealment by competing nonresistant virus in the same sample. To this end, WHO Antiviral Working Group criteria were used to evaluate whether samples containing different proportions of NAI-susceptible and -resistant influenza B viruses had reduced inhibition by NAIs (47)(48)(49).…”

Section: Inhibitory Activity Of Nais On Mixed Populations Of Nai-suscmentioning

confidence: 99%

Competitive Fitness of Influenza B Viruses with Neuraminidase Inhibitor-Resistant Substitutions in a Coinfection Model of the Human Airway Epithelium

Burnham

Armstrong

Webster

et al. 2015

J Virol

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Influenza A and B viruses are human pathogens that are regarded to cause almost equally significant disease burdens. Neuraminidase (NA) inhibitors (NAIs) are the only class of drugs available to treat influenza A and B virus infections, so the development of NAI-resistant viruses with superior fitness is a public health concern. The fitness of NAI-resistant influenza B viruses has not been widely studied. Here we examined the replicative capacity and relative fitness in normal human bronchial epithelial (NHBE) cells of recombinant influenza B/Yamanashi/166/1998 viruses containing a single amino acid substitution in NA generated by reverse genetics (rg) that is associated with NAI resistance. The replication in NHBE cells of viruses with reduced inhibition by oseltamivir (recombinant virus with the E119A mutation generated by reverse genetics [rg-E119A], rg-D198E, rg-I222T, rg-H274Y, rg-N294S, and rg-R371K, N2 numbering) or zanamivir (rg-E119A and rg-R371K) failed to be inhibited by the presence of the respective NAI. In a fluorescence-based assay, detection of rg-E119A was easily masked by the presence of NAI-susceptible virus. We coinfected NHBE cells with NAI-susceptible and -resistant viruses and used next-generation deep sequencing to reveal the order of relative fitness compared to that of recombinant wild-type (WT) virus generated by reverse genetics (rg-WT): rg-H274Y > rg-WT > rg-I222T > rg-N294S > rg-D198E > rg-E119A Ͼ Ͼ rg-R371K. Based on the lack of attenuated replication of rg-E119A in NHBE cells in the presence of oseltamivir or zanamivir and the fitness advantage of rg-H274Y over rg-WT, we emphasize the importance of these substitutions in the NA glycoprotein. Human infections with influenza B viruses carrying the E119A or H274Y substitution could limit the therapeutic options for those infected; the emergence of such viruses should be closely monitored. Annual vaccination is an effective method for controlling influenza disease. The current FDA-approved quadrivalent seasonal influenza vaccine includes both antigenically distinct hemagglutinin (HA) lineages of influenza B virus (i.e., Yamagata and Victoria) (8, 9). Antiviral treatment is another option for the control of influenza, and the neuraminidase (NA) inhibitors (NAIs) are currently the only class of antivirals approved for prophylaxis and treatment of influenza B virus infections. NAIs limit influenza

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“…Treating influenza with NAIs has become the most popular treatment among primary care doctors. NAIs were introduced to clinical practice in 1999, but so far only zanamivir and oseltamivir have been licensed for use in humans [13]. Unfortunately, viruses resistant to zanamivir and oseltamivir have been generated in vitro and in humans recently [14].…”

Section: Introductionmentioning

confidence: 99%

Antiviral activity of Chongkukjang extracts against influenza A virus in vitro and in vivo

Wei

Cha

Kang

et al. 2015

Journal of Ethnic Foods

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Guidance for clinical and public health laboratories testing for influenza virus antiviral drug susceptibility in Europe

Cited by 28 publications

References 32 publications

Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study

Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study

Competitive Fitness of Influenza B Viruses with Neuraminidase Inhibitor-Resistant Substitutions in a Coinfection Model of the Human Airway Epithelium

Antiviral activity of Chongkukjang extracts against influenza A virus in vitro and in vivo

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