Treurnicht FK, etc.,al. 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. Influenza Other Respir Viruses. 2018 Sep 14.
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.
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.
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