Ukraine Virus Update (Update) (Update)

This is an update to part of my November  2, 2009 post that dealt with the virus outbreak in the Ukraine. Excerpt from: http://www.recombinomics.com/News/11040902/Ukraine_Double.html

 

 The number of infected patients has almost doubled to just under ½ million, compared to the report two days ago (see map).  Hospitalized patients also have spiked higher, to 24K from 15K.  ICU cases are not listed, but 60 on ventilators are.  However, most (37) of those on ventilators are Chernivisti Oblast, but Lviv, which has the most fatalities and cases, has none, suggesting the data is incomplete or there are significant shortages of ventilators.  The number of dead has risen to 81, but media reports describe additional fatalities, include those in the Kiev Oblast.

The explosion of cases again raises concerns that the number of fatalities is significantly higher than the 81 listed.  Media reports have described an equal number of pneumonia fatalities which were not considered flu related.  The basis of these exclusions remains unclear.  Similarly, anecdotal reports suggest the number of fatalities is markedly higher than the 81 in the table.

The rapid rise in reported infections, hospitalizations, and deaths in the past few days raise concerns that the virus is transmitting very efficiently.  Spikes in cases have been reported throughout the northern hemisphere, but the spike in fatalities and the frequency in hemorrhagic cases in Ukraine have raised concerns.

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This is a nasty virus. I will try to keep tracking its progress.

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Update from Recombinomics :  "Recombinomics Commentary 22:54
November 6, 2009
871,037 Influenza/ARI Cases

39,603 Hospitalized

135 Deaths

The above numbers from the latest update from Ukraine (see map) continue to alarm. More than half of the Oblasts and cities listed exceed the epidemic threshold, including Kiev and Kiev Oblast, raising concerns that the increase in case numbers will accelerate.  Moreover, hospitalization of 39,603 raises concerns that the number of deaths will also accelerate, since 11% of hospitalized cases in California died.

Although WHO has suggested that these alarming number may reflect sub-standard medical and housing conditions, the numbers remain alarming.  Mill Hill indicated that at least 15 samples were H1N1 positive, indicating they now have a small database of Ukraine sequences.  Although initial reports indicated there were no "major" changes, which presumably referred to reassortment, and no Tamiflu/Peramivir resistance, further analysis was required to rule out significant changes which were presumably linked to SNPs.

However, because the virus already has demonstrated an ability to cause fatal infections in a disproportionate number of children and previously healthy adults, small changes in the virus could lead to increases in viral load leading to an increase in cytokine storm frequency and hemorrhagic pneumonia, as reported for earlier cases."

It just keeps getting worse.

 

Latest Update: http://www.recombinomics.com/News/11090902/Ukraine_1918.html

 

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1918 RBD Polymorphsm in Ukraine H1N1?
Recombinomics Commentary 04:22
November 9, 2009

The recent explosion of H1N1 cases in Ukraine (see map) has focused attention on sequences linked to the outbreak, especially those in the lungs of patients who developed a cytokine storm.  This hemorrhagic pneumonia has been described previously in other fatal swine flu infections, but that rapid increase in reported deaths in Ukraine has raised concerns that the virus is transmitting more efficiently, or is replicating at higher levels in lung tissue.

These changes are frequently linked to changes in the receptor binding domain (RBD) in the HA protein.  Changes in this domain can affect affinity for receptors and also modify tissue tropism.  The recent expansion of seasonal H3N2 with M2 S31N was linked to two changes in or near the receptor binding domain, S193F and D225N.

Recent isolates from Sao Paulo, Brazil, collected from necropsy tissue from fatal cases had two changes at position 225.  Two of the isolates, A/Sao Paulo/53845/2009 and A/Sao Paulo/53838/2009) had D225N (see list), the same change seen in seasonal H3N2. Interestingly, the swine H1N1 is a triple reassortant with flu genes from swine, humans, and birds.  The human gene is PB1 and it was acquired in swine infected with a human H3N2.  The initial isolates had three human genes, the H3 and N2 as well as the PB1.  Thus, the prior association of the human PB1 in isolates with human H3,may increase the advantage offered by D225N.

However, two other isolates from Sau Paulo, A/Sau Paulo/53225/2009 and A/Sau Paulo/53206/2009, collected from the lungs of fatal cases, had another change at position 225, D225G.  This polymorphism is more widespread and recent isolates have been found in Japan, Italy, and China (see list ).  Moreover this polymorphism has been found in two isolates from the 1918/1919 pandemic, A/New York/1/1918 and A/London/1/1919.  Thus, in 1918 the H1N1 virus usually had a D at position 225, but some of the later isolates had D225G, which parallels the data from the 2009 swine H1N1 isolates.

These RBD changes in recent isolates from Sao Paulo, as well as the presence of D225G in sequences from 1918/1919 raise concerns that the swine H1N1 is adapting to its human host by acquisition of RBD polymorphisms.

The explosion of cases in Ukraine, and delays in the release of sequences from fatal cases in Ukraine is a cause for increasing concern.  Recent accelerations of deaths have been widespread across the northern hemisphere, raising concerns that receptor binding domain changes described above, as well as a third polymorphism at position 225, D225E, (see list) are gaining traction as the swine H1N1 adapts to human hosts.

An update on the Mill Hill sequences and deposit of such sequences at a public database such as GISAID, where Mill Hill recently deposited sequences from Europe, would be useful.