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.
