Showing posts with label Mexico. Show all posts
Showing posts with label Mexico. Show all posts

2011-11-03

Mexico Evaluates Upper Respiratory Swabs from Fatal and Severe Cases with 225A, 225G, 225N & 225V

Sequences discussed in this analysis are variously stored publicly at GenBank and at GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GenBank and from GISAID’s EpiFlu™ Database on which this research is based. A GISAID-generated list is detailed in a linked spreadsheet for completeness in citation.

Last Update
2011-11-03

On 2011-10-27, the Instituto Nacional de Enfermedades Respiratorias from the Centro de Investigacion en Enfermedades Infecciosas of Mexico deposited a group of human pH1N1 sequences at GenBank and GISAID.  The deposit is composed of HA segments, 14 sequence fragments of 232 amino acids (aa38 to aa269), each documenting roughly 41% of a full pH1N1 Hemagglutinin segment.  Various homology to Clade1.Upsilon exists on 5 of the sequences.

This Mexican genetic data supports an investigation entitled, H1N1pdm HA D222 variants associated with severity and mortality in patients during a second wave in Mexico and their pathogenicity in mouse model.  Mexico City, Mexico is the geography indicated on the sequence names.  Each sequence is annotated with gender and isolation source (nasopharyngeal swab), while 12 of the 14 also indicate the subject age.  Subject ages range from 23 to 54 years old, all outside the general severity range for seasonal influenza (under 2 years old or over 60 years old).  The sample dates span 2009-10-01 to 2010-04-05 with no case-level specification of treatment protocol, clinical progression or clinical outcome.

The severity and fatality correlation in cases with polymorphisms at amino acid position 222 (aa225 in H3 numbering) was established very early in the pandemic.  The issue of sample location has been repeatedly posed, with ongoing discussion that samples taken from the lower respiratory tract are more probable to produce valid evidence of aa225 revisions.  This INER deposit, relying entirely on upper respiratory swabs, documents cases where aa225 revisions are found in the upper airway.  The individual details of clinical progression and outcome (severe v. fatal) will establish measurable correlation to the upper respiratory sample location.

Four of the samples show multi-nucleotide ambiguity at amino acid position 225 (contiguous mixed traces, residues 715 and 716) producing a codon of rrT.  That sequencing outcome of rrT demonstrates the presence of wild type D225 with both 225G and 225N, hypermorphism at a single amino acid position.  Overall, ten of the fourteen sequences demonstrate a mixed peak (ambiguity) at one or more nucleotides that build aa225.  MexicoCityINER3_NP_47M_2009_10_15 [EPI341034] illustrates the highly variant nature of the pH1N1 reservoir Receptor Binding Site aa225 with two rare values, 225A and 225V, in a mixture without wild type (D225) and with no additional polymorphisms.

Sequences

. . . . MexicoCityINER14_NP_xF_2010_04_05 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341023
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn71E (GAg) mix wt [H6N1],
. . . . . . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn100D (GAc) [H1N1 Avian Farm],
. . . . . . . . 165N,
. . . . . . . . 181S,
. . . . . . . . 189T,
. . . . . . . . syn198A (GCg) mix wt,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER13_NP_48F_2010_03_25 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341024
. . . . . . . . 6 Polymorphisms (5 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER12_NP_37M_2010_03_23 (
. . . . . . . . GISAID HA EPI341025
. . . . . . . . 2 Polymorphisms (2 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 122R,
. . . . . . . . 225N,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER11_NP_34F_2010_02_09 (
. . . . . . . . GISAID HA EPI341026
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn214K (AAa) [H9N2],
. . . . . . . . . . . . . . . . . . [H13N2 Avian],
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER10_NP_39M_2010_02_09 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341027
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn58C (TGc) [H2N3, H3N8, H4, H6],
. . . . . . . . . . . . . . . . . [H7N3, H7N7],
. . . . . . . . . . . . . . . . . [H9N2, H11],
. . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER8_NP_23F_2009_11_23 (
. . . . . . . . GISAID HA EPI341029
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn106E (GAa) [H1N1 Avian],
. . . . . . . . syn189A (GCc),
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER9_NP_49M_2010_01_18 (
. . . . . . . . GISAID HA EPI341028
. . . . . . . . 1 Polymorphisms (1 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER7_NP_54F_2009_11_09 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341030
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 157T,
. . . . . . . . 165N,
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER6_NP_22F_2009_11_06 (
. . . . . . . . GISAID HA EPI341031
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn106E (GAa) [H1N1 Avian],
. . . . . . . . syn189A (GCc),
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER5_NP_52F_2009_10_27 (
. . . . . . . . GISAID HA EPI341032
. . . . . . . . 1 Polymorphisms (1 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER4_NP_xM_2009_10_16 (
. . . . . . . . GISAID HA EPI341033
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn145K (AAg),
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER3_NP_47M_2009_10_15 (
. . . . . . . . GISAID HA EPI341034
. . . . . . . . 2 Polymorphisms (2 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225A mix,
. . . . . . . . 225V mix,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER2_NP_44F_2009_10_12 (
. . . . . . . . GISAID HA EPI341035
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER1_NP_40M_2009_10_01 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341036
. . . . . . . . 4 Polymorphisms (4 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 165N,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)




Please visit GeneWurx.com for insight into the latest published studies. GeneWurx.com

2011-04-05

HA 230I RBS Polymorphism Potential in Mexico

Current trending indicates a reportable potential for the M230I polymorphism spreading on the Hemagglutinin of PF11. This Receptor Binding Domain change may enhance Vaccine Escape from the currently selected vaccine target candidate, CA/07 X181. 

For those who are following the prediction on February 25, 2010, the pandemic reservoir now shows multiple instances of multiple encodings for 230I.  Model adjustment and data transparency allowed a second set of detailed geographic predictions on 2010-08-09 that have also found traction.

The 230I bearing sequences meeting the prediction are documented in the detailed discussion on Vaccine Escape that demonstrates a 100% change rate in the pandemic influenza (pH1N1) reservoir at the critical HA genetics range between amino acid positions 186 and 248.  95% of the amino acid positions have notated revisions.

Expectations for the M230I polymorphism, that first came to our notice for zoonotic concern on the H5N1 human fatality cluster, have now been revised based on the most current public data.  The GeneWurx RnR model approximates that HA 230I will appear in the PF11 RBS according to the following geographic probabilities.

  • 20% probability in Mexico sampled by 2011-06-30.
  • 55% probability in Mexico sampled by 2011-09-30.
  • 10% or less probability of HA 230I conserving across PF11 by 2011-09-30.
  • 17% probability of HA 230I conserving on one or more Hydrae by 2011-09-30.

These probabilities will be updated as additional data is made public.  Transparency at this post-pandemic stage is essential to formulate viable responses for the risk groups.  Release of sequences and clinical data of a finer detail and higher quantity will allow information-based decisions.



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2010-09-24

Pandemic Influenza and Avian Influenza Conjunctivitis Presentation

Last Updated 2010-09-30

Large outbreaks of eye inflammation (conjunctivitis), including hemorrhagic conjunctivitis, have begun around the world this month with several regions registering case counts in the thousands.  Viral infection is frequently associated with this type of highly contagious "Pink Eye" or "Red Eye".  Early pandemic H1N1 cases document these types of eye redness in the patient symptomology.


One recent HA polymorphism found in the pandemic reservoir has been previously associated with viral conjunctivitis with and without classic influenza symptoms. The amino acid value of HA 188T is strongly correlated to conjunctivitis on the Netherlands human H7N7 outbreak during 2003, including zoonoses from commercial poultry operatons. One human fatality was recorded during that outbreak and that case sequence shows the HA 188T.
The 6 pH1N1 sequences that carry 188T (all recent) also demonstrate a significant set of markers with homology to zoonotic serotypes including further H7N7 amino acid homology and extensive H7N7 SNP potential. H9N2 and H3N8 also are potential contributors, but the data sparsity inclines our team to be more concerned with an H7N7 / H9N2 team coordination from commercial domestic poultry operations.

Avian influenza again may be communicating with the human pandemic H1N1 Hydrae. India today, 2010-09-30, is on record in a section of Mumbai as counting 2,500 cases of conjunctivitis this month.  HA 188T is also found in India.

. . . . Florida14_24M_2010_08_05 (
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . syn161Y [H3N8 2009, H6N1, H9N2],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 442I mix,
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . OZVictoria512_2010_07_30 (
. . . . . . . . syn60I,
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn285P,
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . Thailand34_9912_2010_07_14 (
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 200T,
. . . . . . . . HA truncated after aa253)

. . . . Thailand34_9937_2010_07_14 (
. . . . . . . . 162Q [Unique to PF11 GenBank/GISAID],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . HA truncated after aa253)

. . . . NZChristchurch15_2010_07_12 (
. . . . . . . . 100N,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

 . . . . India5107_2010_06_28 (
. . . . . . . . syn60I,
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . syn135V,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . India8910_2010_05_08 (
. . . . . . . . syn49G [H7N3, H7N7],
. . . . . . . . syn51A,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . swThaiCURA75_2010_01 (
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 263D,
. . . . . . . . syn350G [H7N3, H7N7],
. . . . . . . . 414I,
. . . . . . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11])

The human post-pandemic reservoir continues to diversify and augment from a wide variety of avian, canine and equine sources. Sampling and sequence confirmation may corroborate that Mexico, China or Pakistan has HA 188T in the PF11 reservoir near the same geographies where the eye symptoms are occurring.




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