Oseltamivir‐resistant influenza A(H1N1)pdm09 virus associated with high case fatality, India 2015

Influenza A viruses has been associated with severe global pandemics of high morbidity and mortality with devastating impact on human health and global economy. India witnessed a major outbreak of influenza A(H1N1)pdm09 in 2015. This study comprises detailed investigation of cases died of influenza...

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Bibliographic Details
Published in:Journal of medical virology 2018-05, Vol.90 (5), p.836-843
Main Authors: Tandel, Kundan, Sharma, Shashi, Dash, Paban Kumar, Parida, ManMohan
Format: Article
Language:English
Subjects:
Adult
Aged
Amino Acid Substitution
Antiviral Agents - pharmacology
Antiviral drugs
Disease Outbreaks
Drug resistance
Drug Resistance, Viral
Fatalities
Female
Gene sequencing
genetic variation
Genotype
Global economy
Humans
Impact analysis
India - epidemiology
Infections
Influenza
Influenza A
Influenza A Virus, H1N1 Subtype - drug effects
Influenza A Virus, H1N1 Subtype - isolation & purification
influenza virus
Influenza, Human - epidemiology
Influenza, Human - mortality
Influenza, Human - virology
Male
Middle Aged
Morbidity
Mortality
Mutation
Mutation, Missense
mutation/mutation rate
Neuraminidase - genetics
neuraminidase inhibitor
Oseltamivir
Oseltamivir - pharmacology
Pandemics
pandemics, resistance
Patients
Polymorphism, Restriction Fragment Length
Reverse Transcriptase Polymerase Chain Reaction
RNA, Viral - genetics
Sequence Analysis, DNA
Strains (organisms)
Substitutes
Viral Proteins - genetics
Virology
Viruses
Young Adult
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Summary:Influenza A viruses has been associated with severe global pandemics of high morbidity and mortality with devastating impact on human health and global economy. India witnessed a major outbreak of influenza A(H1N1)pdm09 in 2015. This study comprises detailed investigation of cases died of influenza A(H1N1)pdm09 virus infection during explosive outbreak of 2015, in central part of India. To find out presence of drug resistant virus among patients who died of influenza A(H1N1)pdm09 virus infection and to find out presence of other mutations contributing to the morbidity and mortality. Twenty‐two patients having confirmed influenza A(H1N1)pdm09 infection and subsequently died of this infection along with 20 non fatal cases with influenza A(H1N1)pdm09 infection were included in the study. Samples were investigated through RT‐PCR/RFLP analysis, followed by nucleotide cycle sequencing of whole NA gene for detection of H275Y amino acid substitution in NA gene responsible for oseltamivir drug resistance. Out of 22 fatal cases, 6 (27.27%) were found to harbor oseltamivir resistant virus strains, whereas the H275Y mutation was not observed among the 20 non fatal cases. Amino acid substitution analysis of complete NA gene revealed V241I, N369K, N386K substitution in all strains playing synergistic role in oseltamivir drug resistance. High morbidity and mortality associated with influenza A(H1N1)pdm09 viruses can be explained by presence of drug resistant strains circulating in this outbreak. Presence of Oseltamivir resistant influenza A(H1N1)pdm09 viruses is a cause of great concern and warrants continuous screening for the circulation of drug resistant strains.
ISSN:0146-6615
1096-9071
DOI:10.1002/jmv.25013