Rhiza Labs FluTracker Forum

Pandemic H1N1
One hundred and eighty samples were propagated for antigenic analysis; only a single virus showed an 8-fold drop in HI titre with the ferret antiserum directed against A/California/7/2009.

Many recent isolates have grouped within two sub-clades. One sub-clade is defined by a substitution at amino acid 125 (with additional substitutions at amino acid residues 94 and 250 being observed in several viruses, represented by A/Christchurch/16/2010). The second sub-clade carries substitutions at residues 128, 199 and 295 of the HA, represented by A/Hong Kong/2213/2010, with additional substitutions at residues 163 and 271 in a sub-set of viruses.

Fewer low reactors have been detected in 2010 than was observed in 2009.

New genetic sub-clades have been detected but they do not appear antigenically distinct from the majority of A(H1N1) pandemic 2009 viruses collected since the start of the pandemic.

Genetic subgroup represented by A/Christchurch/16/2010
Genetic subgroup represented by A/Hong Kong/2213/2010

H3N2
Several new genetic (H3N2) sub-clades of the Victoria/208 clade have emerged but we have no conclusive evidence to indicate that the observed genetic changes have resulted in a change in antigenicity.

Influenza B
Influenza B viruses of the Victoria-lineage continued to predominate over those of the Yamagata-lineage.

In the Victoria-lineage many viruses yielded reduced titres with anti-sera raised against the egg-grown vaccine virus. Anti-sera raised against reference strains isolated and propagated in mammalian cells continued to react well with recently isolated viruses. There have been only a small number of amino acid substitutions in recently isolated viruses in comparison with the current vaccine virus.

There was little evidence of antigenic change compared with reference strains in the small number of viruses of the B/Yamagata-lineage that were analysed.

Antiviral Resistance
In total 1766 viruses were assayed, 1477 H1N1 pandemic, 167 H3N2, 22H1N1 seasonal and 100 influenza B. Of these just 7 (0.4%) H1N1 pandemic and 22 (100%) H1N1 seasonal viruses were oseltamivir resistant, all due to H275Y substitution in NA, and all viruses (1766)remained sensitive to zanamivir. (All) 7 H1N1 pandemic oseltamivir-resistant viruses were related to drug use in either prophylaxis or treatment settings.

No other resistance markers were observed in NA genes of all influenza types/subtypes and, for H1N1 pandemic viruses, all NA genes encoded I223 indicative of retained susceptibility to oseltamivir and zanamivir (I223R substitution has been associated with reduced susceptibility to both oseltamivir and zanamivir).

Among the 1477 H1N1 pandemic viruses assayed phenotypically, just 4 viruses showed decreased susceptibility to oseltamivir and/or zanamivir. These 4 viruses were derived from countries with little/no NI drug use. A number of the amino acid substitutions occurring in the NAs of these 4 viruses were in the stalk region of NA, but all contained at least one substitution that could result in the reduced susceptibility: K262R and I396V (A/Georgia/4032/2009), Y274H (A/Livadia/1851/2010), S105N and I263V (A/Argos/2231/2010), D199G and R257K (A/Volgda/3/2010)
.
Substitutions at positions 105 and 262 have been associated with reduced NI susceptibility in N1 containing viruses of avian origin.

M2-inhibitors (amantadine and rimantadine), full M gene sequencing has shown 100% resistance in H1N1 pandemic and H3N2 viruses due to the S31N substitution in the M2 protein, while H1N1 seasonal viruses remained susceptible.

H1pdm viruses with reduced susceptibility to Oseltamivir and Zanamivir
Virus, Collection Date. IC50*

A/Georgia/4032/09. 12/09/09, 4.85, 3.23
A/Livadia/1851/10, 01/26/10, 6.39, 2.96 (has H274)
A/Argos/2231/10, 02/03/10, 4.41, 1.33
A/Volgda/3/10, 03/15/10, 11.80, 16.68
* IC50 values are normally <2.0 and <1.0 nM for Oseltamivir and Zanamivir respectively

Summary of clinical samples and isolates received, collected between January and August 2010

29 Countries submitted samples

H1N1pdm: 394 samples, 180 propagated
H3N2: 55 samples, 17 prop.
B Victoria: 100 samples, 74 prop.
B Yamagata: 13 samples, 10 prop.

Respiratory Syncytial Virus (RSV)
An additional effect (of panflu) has been on the timing of Respiratory Syncytial Virus (RSV) activity compared to the preceding three seasons. RSV activity preceded influenza activity in the three previous seasons but in 2009/10 RSV activity was delayed although numbers of detections ultimately approached those observed in the three previous seasons and in all four seasons RSV detections effectively ceased by week 20. The reasons for this are not clear.

http://www.nimr.mrc.ac.uk/documents/abo ... p-2010.pdf

For earlier yearly and interim reports:
http://www.nimr.mrc.ac.uk/who-influenza ... m-reports/

[quote="issapharma"]
Antiviral Resistance
In total 1766 viruses were assayed, 1477 H1N1 pandemic, 167 H3N2, 22H1N1 seasonal and 100 influenza B. Of these just 7 (0.4%) H1N1 pandemic and 22 (100%) H1N1 seasonal viruses were oseltamivir resistant, all due to H275Y substitution in NA, and all viruses (1766)remained sensitive to zanamivir. (All) 7 H1N1 pandemic oseltamivir-resistant viruses were related to drug use in either prophylaxis or treatment settings.

[quote]

That's a tiny number showing Tamiflu resistance from a sequence analysis only a few months ago, and all related to prior Tamiflu resistance.

Seems Tamiflu resistance in swine flu was not an issue before these recent mutations.

Is there a more up date equivalent set of data from the UK?

The analysis is primative. They are not detecting sub-populations unless the patient is treated with Tamiflu.

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Thanks. Any more recent and more sophisticated equivalent reports available?

From memory, in all that long UK thread I can't recall any stories about patients being given Tamiflu which failed (although they probably aren't using it much). In comparison, there seems to be lots of stories about people who have either had pH1N1 before or had a vax, and have now got the new version again now.

They have acknowledge H274Y in patients that have not been treated, a major signal that H274Y is transmitting.

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www.twitter.com/hniman