Detection of Influenza Viruses Resistant to Neuraminidase Inhibitors in Global Surveillance during the First 3 Years of Their Use

Monto, Arnold S.; McKimm-Breschkin, Jennifer L.; Macken, Catherine A.; Hampson, Alan W.; Hay, Alan J.; Klimov, Alexander; Tashiro, Masato; Webster, Robert G.; Aymard, M; Hayden, Frederick G.; Zambon, Maria

doi:10.1128/aac.01339-05

Cited by 345 publications

(342 citation statements)

References 30 publications

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“…This observation was expected because zanamivir and laninamivir share structural similarity 38. Earlier surveillance studies7, 39 used box‐and‐whisker plot analyses to identify two kinds of outliers, mild (1·5–3 IQR from the 25th and 75th percentiles) and extreme (3 IQR from the 25th and 75th percentiles and at least >10‐fold mean IC 50 ). Another study40 using box‐and‐whisker plot analysis identified outliers based on IC 50 1·5 IQR from the 25th and 75th percentiles, while in another study,41 isolates with IC 50 values outside the 95% confidence limits (mean IC 50 ± 2 SD) were characterized as outliers.…”

Section: Discussionmentioning

confidence: 94%

“…Resistance to NAIs among influenza viruses circulating worldwide was previously low (<1%),7, 8 but during the 2007–2008 season, a dramatic emergence of oseltamivir‐resistant seasonal influenza A(H1N1) viruses with the H275Y mutation in the NA occurred 9, 10, 11, 12, 13. By the 2008–2009 season, many countries were reporting up to 100% oseltamivir resistance among seasonal influenza A(H1N1) viruses 14, 15.…”

Section: Introductionmentioning

confidence: 99%

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Neuraminidase inhibitor susceptibility surveillance of influenza viruses circulating worldwide during the 2011 Southern Hemisphere season

Okomo-Adhiambo

Sleeman

Lysen

et al. 2013

Influenza Resp Viruses

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BackgroundNeuraminidase (NA) inhibitors (NAIs) are currently the only antivirals effective against influenza infections due to widespread resistance to M2 inhibitors.MethodsInfluenza A and B viruses (n = 1079) collected worldwide between April 01, 2011, and September 30, 2011, were assessed for susceptibility to FDA‐approved NAIs, oseltamivir and zanamivir, and investigational peramivir, using the fluorescent‐based NA‐Fluor™ Influenza Neuraminidase Assay Kit. A subset of viruses (n = 98) were tested for susceptibility to the investigational NAI, laninamivir.ResultsInfluenza A(H1N1)pdm09 viruses (n = 326) were sensitive to all NAIs, except for two (0·6%) with H275Y (N1 numbering; H274Y in N2 numbering) substitution, which exhibited elevated IC 50s for oseltamivir and peramivir, and a third with previously unreported N325K substitution, exhibiting reduced susceptibility to oseltamivir. Influenza A(H3N2) viruses (n = 407) were sensitive to all NAIs. Influenza B viruses (n = 346) were sensitive to all NAIs, except two (0·6%) with H273Y (N1 numbering; H274Y in N2 numbering) substitution, exhibiting reduced susceptibility to oseltamivir and peramivir, and one with previously unreported G140R and N144K substitutions, exhibiting reduced susceptibility to oseltamivir, zanamivir, and peramivir. All influenza A and B viruses were sensitive to laninamivir. It is unknown whether substitutions N325K, G140R, and N144K were present in the virus prior to culturing because clinical specimens were unavailable for testing.ConclusionsThis study summarizes NAI susceptibility of influenza viruses circulating worldwide during the 2011 Southern Hemisphere (SH) season, assessed using the NA‐Fluor™ Kit. Despite low resistance to NAIs among tested influenza viruses, constant surveillance of influenza virus susceptibility to NAIs should be emphasized.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Neuraminidase inhibitor susceptibility surveillance of influenza viruses circulating worldwide during the 2011 Southern Hemisphere season

Okomo-Adhiambo

Sleeman

Lysen

et al. 2013

Influenza Resp Viruses

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“…In recent years, the human influenza A viruses have developed complete resistance to an older class of drugs, the adamantanes, indicating the ability of these viruses to develop and subsequently maintain resistance to antivirals 3. In the first years of NAIs usage, following their introduction in 1999, naturally occurring resistance was sporadically reported and a very limited number of cases were described 4, 5, 6, 7. However, in 2008, naturally occurring oseltamivir resistance was detected among seasonal H1N1 viruses in Norway 8.…”

Section: Introductionmentioning

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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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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“…Box-and-whisker plot analysis was performed to identify potential outliers for NAI susceptibility (15). All viruses defined as resistant to oseltamivir (IC 50 Ͼ 100 nmol/liter) were removed prior to analysis.…”

Section: Methodsmentioning

confidence: 99%

Adamantane- and Oseltamivir-Resistant Seasonal A (H1N1) and Pandemic A (H1N1) 2009 Influenza Viruses in Guangdong, China, during 2008 and 2009

et al. 2011

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Detection of Influenza Viruses Resistant to Neuraminidase Inhibitors in Global Surveillance during the First 3 Years of Their Use

Abstract: Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs

Cited by 345 publications

References 30 publications

Neuraminidase inhibitor susceptibility surveillance of influenza viruses circulating worldwide during the 2011 Southern Hemisphere season

Neuraminidase inhibitor susceptibility surveillance of influenza viruses circulating worldwide during the 2011 Southern Hemisphere season

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

Adamantane- and Oseltamivir-Resistant Seasonal A (H1N1) and Pandemic A (H1N1) 2009 Influenza Viruses in Guangdong, China, during 2008 and 2009

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