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

Abstract

BACKGROUND : Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) are 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 quantitative polymerase chain reaction (qPCR). Drug susceptibility was determined by chemiluminescence-based NA-STAR/ NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance. RESULTS : Forty percent (6341/15 985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. A total of 1236/6341 (19.5%) virus isolates were generated of which 307/1236 (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 nmol/L (range 0.01-3.60) in 2007 to 73 nmol/L (range 1.56-305 nmol/L) in 2008. Influenza A isolates from 2009 to 2013 were susceptible to oseltamivir [A(H3N2) median IC50 = 0.05 nmol/L (range 0.01-0.08); A(H1N1)pdm09 = 0.11 nmol/L (range 0.01-0.78)] and zanamivir [A(H3N2) median IC50 = 0.56 nmol/L (range 0.47-0.66); A(H1N1)pdm09 = 0.35 nmol/L (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.