Friday, March 30, 2018

Russia's Late Season Flu Surge Continues - More Resistant H1N1pdm In Moscow

Cumulative Flu Subtypes This Season


Russia saw an unusually late start to their influenza season this winter, passing their epidemic threshold for the first time in mid-February (week 6), only to fall below that threshold four weeks later (week 10). 
That drop (possibly due to a lack of reporting) was short-lived, as the rate of flu jumped markedly the following week and continues to rise with this week's report.
All of this is a bit out of character, as we saw reported last January in Eurosurveillance: Changes In Timing Of Influenza Epidemics - WHO European Region 1996-2016, over the past 2 decades Russia's flu seasons have tended to peak earlier with each passing year.
Due to its 6,000 mile wide expanse and varied climate, Russia often sees a very complex flu season, with many areas experiencing different mixes of flu subtypes, and much different epidemic onset dates (see map above).
While still highly variable by region, over the past couple of months we've seen the dominant flu strain in Russia shift from A(H3N2) to A(H1N1)pdm, with Influenza B making a late season surge. 

Also of note, this week Russia National Influenza Centre (RII NIC) is reporting on two more Moscow isolates found to be resistant to NAI (Neuraminidase Inhibiting) antiviral drugs. 
Five weeks ago, in Russia : A Late Season Flu Surge & 3 NAI Resistant H1N1 Viruses, we saw the initial report on resistant viruses carrying the H275Y mutation in Moscow.
This week's report only references a total of 19 isolates (8 H1N1pdm, 4 H3N2, and 7 Influenza B) having been tested for resistance this winter, with 5 of 8 H1N1 isolates (62%) - all from Moscow - showing significant resistance to NAI antivirals.
By contrast, the CDC has tested more than 700 H1N1pdm viruses this winter, and has found only 9 (1.3%) showing signs of  NAI resistance - a percentage that has been fairly steady since the virus emerged in 2009.
On the face of it, today's report makes it look as if 100% of the H1N1pdm  viruses tested from Moscow this winter have shown resistance - and that would be concerning - but what we don't know is their criteria for testing viruses for resistance (or if they really only tested 5 isolates from Moscow).
If they are doing targeted testing - say of patients receiving antivirals who are not responding to treatment - then a high rate of resistance would be expected.
If these are random tests, then 5 out of 5 H1N1pdm viruses turning up NAI resistant (assuming that is the correct ratio) from Moscow is a pretty big deal. Pending the receipt of more solid information,  or similar reports from outside of Russia, I'm filing this under `curious' and something to definitely keep an eye on.
Although a late arriving Russian flu season is far from unheard of, given the atypical flu epidemics we've been seeing the past 12 months around the globe (summer H3N2 outbreaks in Hong Kong & China, followed by Influenza B this winter, and back-to-back H3N2 seasons in the Northern Hemisphere), the current flu situation in Russia is worth following.
Some excerpts from this week's Russian Influenza Epidemiological Report (Week 12) follow:

Influenza and ARI morbidity data.  Increase of influenza and other ARI activity was registered during week 12.2018 in Russia. The ILI & ARI incidence rate (96.3 per 10 000 of population) was above by 32.7% the nationalwide baseline.

Etiology of ILI & ARI morbidity. The overall percent of respiratory samples positive for influenza was estimated as 29.1%. Proportion of influenza A(H1N1)pdm09, A(H3N2), type A and type B viruses was estimated as 38.6%, 22.9%, 5.5% and 33.0%, respectively.

Antigenic characterization. 255 influenza viruses were characterized antigenically in Moscow and Saint-Petersburg NICs, including 69 influenza A(H1N1)pdm09 viruses, 54 influenza A(H3N2) strains and 132 influenza type B strains. 

All influenza A(H1N1)pdm09 strains were related to influenza A/Michigan/45/2015, influenza A(H3N2) strains to A/Hong Kong/4801/2014 viruses. 126 influenza type B strains belonged to Yamagata lineage and were like B/Phuket/3073/2013 reference virus, 6 influenza type B strains belonged to Victoria lineage and were antigenically related to B/Brisbain/60/2008 strain.

Genetic characterization.
Full-genome NGS of 58 influenza positive samples and viruses from 6 cities was conducted. 16 influenza A(H1N1)pdm09  viruses belonged to phylogenetic group 6B.1 with amino acid substitutions in HA S84N, S162N and I216T. 

According to phylogenetic analisis of HA 18 of 22 tested influenza A(H3N2) viruses belonged to clade 3C.2a carring aa substitutions L3I, N144S, F159Y, K160T, N225D and Q311H in HA1. Four influenza A(H3N2) viruses belonged to genetic subgroup 3C.2a1 and carried aa substitutions K92R, N121K, T135K and H311Q.

2 influenza B viruses of Victoria-lineage belonged to genetic subgroup 1A (B/Brisbane/60/2008-like). All 18 influenza B viruses of Yamagata-lineage belonged to clade 3 (B/Phuket/3073/2013-like) and had substitution L172Q and M251V in HA1.

Susceptibility to antivirals. Most viruses were susceptible to NA inhibitors excluding 5 influenza A(H1N1)pdm09 strains isolated in Moscow which had H275Y amino acid substitution in NA responsible for highly reduced susceptibility to oseltamivir and zanamivir.
14 influenza strains tested in MUNANA-assay for antiviral resistance to NA inhibitors in RII NIC, including 3 A(H1N1)pdm09 strains isolated in St.Petersburg, 4 A(H3N2), two B Victoria strains and 5 B Yamagata viruses were susceptible to oseltamivir and zanamivir. All influenza A strains tested were resistant to rimantadine.
Percent of positive ARI cases of non-influenza etiology (PIV, adeno- and RSV) was estimated as 21.4% of investigated patients by IFA and 6.0% by PCR. Last weeks RSV dominated among ARI agents.

In sentinel surveillance system clinical samples from 127 SARI and ILI/ARI patients were investigated by rRT-PCR. 27 (47.4%) influenza cases were detected among SARI patients, including 6 influenza A(H1N1)pdm09 cases, 11 influenza A(H3N2) cases and 10 influenza B cases. Among ILI/ARI patients 27 (38.6%) influenza cases were detected, including 9 influenza A(H1N1)pdm09, 13 influenza A(H3N2) and 5 influenza B cases.

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