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Influenza Other Respir Viruses. 2018 Sep 14. doi: 10.1111/irv.12611. [Epub ahead of print]
Replacement of neuraminidase inhibitor susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africa.
Treurnicht FK1, Buys A1, Tempia S2,3, Seleka M1, Cohen AL2,4, Walaza S1,5, Glass AJ6, Rossouw I7, McAnerney J1, Blumberg L8,5, Cohen C1,5, Venter M9,10.
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Abstract
BACKGROUND:
Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) is scarce, and no extensive analysis was done.
OBJECTIVES:
We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa.
PATIENTS/METHODS:
We enrolled participants through national influenza-like illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and real-time polymerase chain reaction (qPCR). Drug susceptibility was determined by chemilluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance.
RESULTS:
Forty percent (6,341/15,985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. 1,236/6,341 (19.5%) virus isolates were generated of which 307/1,236 (25%) were tested for drug susceptibility. During 2007-2008 the median 50% inhibitory concentration (IC50 ) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nM (range 0.01-3.60) in 2007 to 73 nM (range 1.56-305 nM) in 2008. Influenza A isolates from 2009-2013 were susceptible to oseltamivir [A(H3N2) median IC50 = 0.05 nM (range 0.01-0.08); A(H1N1)pdm09= 0.11 nM (range 0.01-0.78)] and zanamivir [A(H3N2) median IC50 = 0.56 nM (range 0.47-0.66); A(H1N1)pdm09= 0.35 nM (range 0.27-0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009-2013.
CONCLUSIONS:
We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained susceptible to NAIs; therefore these drugs are useful for treating influenza-infected patients. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
South Africa; influenza; oseltamivir; susceptibility
PMID: 30218485 DOI: 10.1111/irv.12611
Free full text
Replacement of neuraminidase inhibitor susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africa.
Treurnicht FK1, Buys A1, Tempia S2,3, Seleka M1, Cohen AL2,4, Walaza S1,5, Glass AJ6, Rossouw I7, McAnerney J1, Blumberg L8,5, Cohen C1,5, Venter M9,10.
Author information
Abstract
BACKGROUND:
Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) is scarce, and no extensive analysis was done.
OBJECTIVES:
We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa.
PATIENTS/METHODS:
We enrolled participants through national influenza-like illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and real-time polymerase chain reaction (qPCR). Drug susceptibility was determined by chemilluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance.
RESULTS:
Forty percent (6,341/15,985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. 1,236/6,341 (19.5%) virus isolates were generated of which 307/1,236 (25%) were tested for drug susceptibility. During 2007-2008 the median 50% inhibitory concentration (IC50 ) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nM (range 0.01-3.60) in 2007 to 73 nM (range 1.56-305 nM) in 2008. Influenza A isolates from 2009-2013 were susceptible to oseltamivir [A(H3N2) median IC50 = 0.05 nM (range 0.01-0.08); A(H1N1)pdm09= 0.11 nM (range 0.01-0.78)] and zanamivir [A(H3N2) median IC50 = 0.56 nM (range 0.47-0.66); A(H1N1)pdm09= 0.35 nM (range 0.27-0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009-2013.
CONCLUSIONS:
We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained susceptible to NAIs; therefore these drugs are useful for treating influenza-infected patients. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
South Africa; influenza; oseltamivir; susceptibility
PMID: 30218485 DOI: 10.1111/irv.12611
Free full text