Table 3.
Frequency of amino acid substitutions in NAs, submitted to GISAID and NCBI sequence databases, known to occur clinically but currently of unknown impact, that cause reduced sensitivity in vitro.a
| Type/subtype | NA amino acid substitutionb | No. of sequences containing the substitution (%)c | Home country patient (n) | Included in phenotypic analysisd |
|---|---|---|---|---|
| A(N1) | D199N | 25 (1.9 %) | Bulgaria (7) | Yes (NI) |
| Dominican Republic (1) | Yes (NI) | |||
| Georgia (1) | Yes (NI) | |||
| Germany (1) | Yes (NI) | |||
| Italy (1) | No | |||
| Italy (2) | Yes (NI) | |||
| Japan (2) | Yes (NI) | |||
| Latvia (1) | Yes (NI) | |||
| Malaysia (1) | Yes (NI) | |||
| Poland (2) | No | |||
| United Kingdom (1) | No | |||
| United States (5) | Yes (NI) | |||
| I223R | 2 (0.2%) | Belgium (1) | No | |
| Malaysia (1) | Yes (RI to oseltamivir) | |||
| N295S | 0 | |||
| A(N2) | E119V | 2 (0.2%) | United Kingdom (1) | Yes (NI) |
| United States (1) | Yes (HRI to oseltamivir) | |||
| R292K | 0 | |||
| N294S | 0 | |||
| Be | R150K | 0 | ||
| D197E | 0 | |||
| D197N | 4 (0.5%) | China (HA Yam/NA Vic) (1) | Yes (RI to zanamivir and oseltamivir) | |
| China (HA Yam/NA Yam) (1) | No | |||
| Japan (HA Yam/NA Yam) (1) | Yes (RI to zanamivir, oseltamivir, peramivir and laninamivir) | |||
| Japan (HA Yam/NA Yam) (1) | Yes (RI to oseltamivir and peramivir) | |||
| I221T | 0 | |||
| N294S | 0 | |||
| G407S | 0 |
As listed in the table on the WHO website, available at: http://www.who.int/influenza/gisrs_laboratory/antiviral_susceptibility/nai_overview/en/; accessed 15 January 2015.
Amino acid position numbering is A subtype and B type specific.
Percentage based on the number of sequences in the final data set after curation – see Supplementary Table 2.
Yes indicates that the virus was analysed by a WHO CC. NI = normal inhibition; RI = reduced inhibition; HRI = highly reduced inhibition, assessed by in vitro assay for the neuraminidase inhibitors (NAIs) indicated.
The H273Y substitution found in the WHO CC data was not included here, because it did not fulfil the requirements for screening: a new substitution should be present in the clinical specimen and more than a single occurrence if in a patient who has not been treated with a NAI.