2011-01-10

UK Severe Wave Sequences Show No Fatalities with 225G

Last Updated 2011-01-12

The UK Health Protection Agency released a group of 37 sequences at GISAID dated 2010-01-05 that appeared sometime after that date. Some of the sequences in this deposit also appear on the Figure 3 Phylogenetic Tree from the HPA Eurosurveilance paper requested to be cited as:

Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1):pii=19760.
Available online:
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760
Date of submission: 31 December 2010

The science community expected a full deposit to back the paper, but not all sequences noted on the phylogenetic table were in place at GISAID as of this 2nd deposit.

The recent GISAID deposit added 4 of the fatalities noted on the Ellis Figure3 1 phylogenetic tree to the 4 fatalities previously released on 2010-12-20.  The previously released sequences were not marked at GISAID with a fatality notation, but now have been notated as "Deceased" as of yesterday.  Oddly enough, on the 2010-01-05 deposit, none of the sequences notated as fatal on the phylogenetic tree were marked as to outcome at GISAID?  This dys-synchronicity and cycling of outcome data is less than optimal for worldwide communication.

None of the sequences at the GISAID database that correspond to notated fatalities on the Eurosurveillance paper carry the severity marker of HA 225G.

225G is found on identical HA sequences noted as 2 severe cases.
  • UKEngland4940476_2010_12
  • UKEngland4880378_2010_12
. . . . UKEngland4940476_2010_12 (
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg) [Regional Marker 2009 (tTA)]
. . . . . . . . . . . . . . . . . . . . [TexasAF2588_2009_10_04,
. . . . . . . . . . . . . . . . . . . . TexasJMS404_2010_01_08],
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L [Regional Marker 2009]
. . . . . . . . . . . . . . . [UKEngland4880378_2010_12 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland4640543_2010_11_f with syn179L, 188T, 190G
. . . . . . . . . . . . . . . UKEngland4920303_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland142_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland4860049_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland126_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . NZChristchurch8_2010_07_08
. . . . . . . . . . . . . . . . . . . with syn44L, 97N, syn99I, syn106E, 128D,
. . . . . . . . . . . . . . . . . . . . . . . syn214K, 253A, syn362S, 377K,
. . . . . . . . . . . . . . . Calif06_2010_04_05 with 269V
. . . . . . . . . . . . . . . Hawaii08_2010_04_12
. . . . . . . . . . . . . . . . . . . with 159D, 269V, 312R, 313K,
. . . . . . . . . . . . . . . Ethiopia13_2010_02_10
. . . . . . . . . . . . . . . . . . . with 100N, syn163K, 269V, 324I, syn360Q, syn455Q,
. . . . . . . . . . . . . . . Philippines824_2010_02_17 with 165N,
. . . . . . . . . . . . . . . Kosova876_2009_12_22,
. . . . . . . . . . . . . . . RussiaYakutsk_EAV_2009_11_18,
. . . . . . . . . . . . . . . Netherlands2143_2009_11_16 with syn179L (tTA),
. . . . . . . . . . . . . . . RussiaYaroslavl_CHMV_2009_11_10_f with 224K & 225G mix
. . . . . . . . . . . . . . . AntwerpINS221_2009_10_28 with syn179L (tTA)],
. . . . . . . . 454N)

. . . . UKEngland4880378_2010_12 (
. . . . . . . . 100N,
. . . . . . . . syn179L,
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

With 8 fatalities noted on the tree and none of them coming from cases manifesting an HA 225G severity marker, we must ask for more data while looking elsewhere for causality.  The common theme in recent UK and other geographies is hyper-zoonosis creating divergency.  Animal reservoirs (H3N8, H5N1, H7N7) carry change values matching the recent intake into the pH1N1 circulation.  Data suggests that this human disease is rapidly diversifying by accumulating genetic information from multiple animal reservoirs.

For example, the 377G that is emergent in 2009 Human H5N1 from Dakahlia, Egypt is also emergent in England and Iran in the Pandemic H1N1 reservoir. A recent fatal case from England, UKEngland4500186_2010_11_f, carries the same coding for 377G combined with a 190Y that is found only elsewhere in 2010 Malmoe, Sweden pH1N1, in early pH1N1 with HA 157E in Brasil and in Avian H6N1.

. . . . UKEngland4500186_2010_11_f  (
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . 190Y [Avian H6N1],
. . . . . . . . . . [SwedenMalmoe1_2010_01_01_xL
. . . . . . . . . . . . with 377K, syn413K,
. . . . . . . . . . Brasil7450_2009_07_22
. . . . . . . . . . . . with 157E mix wt],
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . . . . . . [IranBandarAbbas5096_2010_10_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C,
. . . . . . . . . . . . . Florida13_2010_08_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C, 512M,
. . . . . . . . . . . . . . Iowa05_2010_05_04
. . . . . . . . . . . . . . . . . . . with 208K, syn516I,
. . . . . . . . . . . . . . swSouthDakota1_2010_04_27,
. . . . . . . . . . . . . . TexasAF2647_2010_04_11
. . . . . . . . . . . . . . . . . . . with 200S, syn214K, syn276H,
. . . . . . . . . . . . . . swIowa02999_2010_04_01,
. . . . . . . . . . . . . . UtahAF2653_2010_03_14
. . . . . . . . . . . . . . . . . . . with syn253V,
. . . . . . . . . . . . . . North Carolina05_2010_02_24
. . . . . . . . . . . . . . . . . . . with 259V,
. . . . . . . . . . . . . . Kentucky04_2010_02_22
. . . . . . . . . . . . . . . . . . . with syn488D,
. . . . . . . . . . . . . . Minnesota02_2010_02_17
. . . . . . . . . . . . . . . . . . . with 259V, 509D,
. . . . . . . . . . . . . . SouthCarolina01_2010_01_27
. . . . . . . . . . . . . . . . . . . with syn238E, syn488D,
. . . . . . . . . . . . . . AnasPlatBelgium04328_pcs17_2010_01_21
. . . . . . . . . . . . . . . . . . . with syn474C,
. . . . . . . . . . . . . . GermanyAF2208_2010_01_20
. . . . . . . . . . . . . . . . . . . with #1T, 225E,
. . . . . . . . . . . . . . NorthCarolina03_2010_01_20
. . . . . . . . . . . . . . . . . . . with 225G mix, 259V, syn275V,
. . . . . . . . . . . . . . NewMexico01_2010_01_05
. . . . . . . . . . . . . . . . . . . with 430I, syn445V, syn490P,
. . . . . . . . . . . . . . swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . with #1T, 0A, 189T, syn338G,
. . . . . . . . . . . . . . . . . . . . . . syn451K, syn474C, syn456L, syn529L,
. . . . . . . . . . . . . . Moldova5053_2009_12_11
. . . . . . . . . . . . . . . . . . with 173R, 176I, 225A, 225G mix wt, syn286K,
. . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . with syn297N, syn343G, 471H,
. . . . . . . . . . . . . . KoreaAF2411_2009_11_11
. . . . . . . . . . . . . . . . . . . with 237I, syn286K,
. . . . . . . . . . . . . . England94840077_2009_11
. . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . BahrainN11892_2009_10
. . . . . . . . . . . . . . . . . . . with 208K,
. . . . . . . . . . . . . . Nevada16_2009_10_02
. . . . . . . . . . . . . . . . . . . with 464R mix wt,
. . . . . . . . . . . . . . Tasmania2005_2009_07_03
. . . . . . . . . . . . . . . . . . . with 289M,
. . . . . . . . . . . . . . Texas42303371_2009
. . . . . . . . . . . . . . . . . . . with syn456L, syn507K],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 512M,
. . . . . . . . 530I)

The HPA Ellis Figure3 1 phylogenetic tree did not notate the 377G branch though 5 English sequences, including this fatal one, appear on the chart carrying the H5N1 Human adaptation.

  • UKEngland83_2010_10
  • UKEngland87_2010_10
  • UKEngland5500192_2010_10
  • UKEngland119_2010_11
  • UKEngland4500186_2010_11_f
GeneWurx has annotated the Ellis Figure3 1 phylogenetic tree with green boxes next to the four fatal GISAID 2010-12-20 deposited sequences and has proposed polymorphism notations on various unmarked branches in an attempt to provide clarity.

UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated_2011_01_08.JPG

Is the Hydra Effect providing Immune Escape capacity for this circulating viral reservoir?  Has an accelerant been insinuated into the reservoir?

In many locales around the United Kingdom, half of the ICU beds are occupied by Influenza patients.  Only 1 of 12 ICU beds was occupied by an Influenza patient at the peak of last year's pandemic.  100% of the ECMO capacity (heart/lung machine) has been utilised for more than 2 weeks.  Hospitals have moved to "Black Alert" status.  Ireland has set new records for the number of ER (Casualty, A&E) patients left on gurneys due to room capacity problems. 

Do these facts move the HPA to quickly derive plausible causality and workable next steps?

Usable data streams with matched clinicals to the sequences are the primary inputs required to investigate and validate causality.  An explanation is deserved from the HPA on their removal of this valuable data from the science community?

Supporting Sequences


. . . . Florida13_2010_08_02 (
. . . . . . . . 51T,
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . syn363G,
. . . . . . . . 377G,
. . . . . . . . syn474C,
. . . . . . . . 512M)

. . . . SwedenMalmoe1_2010_01_01_xL (
. . . . . . . . 190Y mix wt [Avian H6N1],
. . . . . . . . 324I,
. . . . . . . . 377K,
. . . . . . . . syn413K)

. . . . Brasil7450_2009_07_22 (
. . . . . . . . 157E mix wt,
. . . . . . . . 190Y [Avian H6N1])


1. Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1):pii=19760. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760


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