Posted on 10/30/2009 4:42:41 AM PDT by Uncle Ike
D225G and D225N In Utah Patient Raises Pandemic Concerns
Recombinomics Commentary 23:55
December 6, 2009
http://www.recombinomics.com/News/12060901/D225G_D225N_Utah.html
The CDC has put HA sequences, A/Utah/42/2009, from a Utah patient (28F) on deposit at Genbank, which has D225G and D225N. Moreover, the sequence from the original sample gives mixed signals at tandem positions, revealing significant heterogeneity that the codon. A clone for the original sample has D225G. D225N and D225G have been identified in necropsy lung samples from Brazil (A Sao Paulo/53845/2009 and A/Sao Paulo/53838/2009 have D225N while A/Sao Paulo/53225/2009 and A/Sao Paulo/53206/2009 have D225G) raising concerns that these polymorphisms are associated with more severe disease.
The severity may be linked to viral load, because D225G and D225N were present as mixtures in early cases in the US in California and Texas. In fact the vaccine target, A/California/7/2009 was a mixture for D225G, as were several other isolates isolated at about the same time in Texas and California. Other isolates in the same areas, as well as New York, did not give mixed signals, but D225G was found in milder cases.
More recently, these changes were found in more severe cases. All four fatal cases in Ukraine had D225G, while the first fatal cases in Norway had D225G and D225E SNPs. The Utah case above however is the first sample with D225G and D225N. In the United States, the two isolates in New York with D225N had an additional polymorphism which was also in A/Ternopil/N11/2009, a fatal case from Ukraine, suggesting additional relationships which are not well represented in the existing database. These relationships may be obscure because of tissue specific expression, and mixtures which are impacted by cloning procedures.
However, the recent findings sequences encoding D225N and D225G, as well as wild type, in the same sample raises concerns that this diversity has paved the way for rapid and varied responses to immunological pressures which has already cause concerns due to the low reactor status of D225G when tested against anti-sera directed against the target of the killed vaccine.
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“Where the hell it got all these genes from we don’t know,” says Robert Webster, “But this is a real super-mixed up virus.”
Patient in Utah has swine flu virus with D225G, low reactor H1N1 mutation causing lung hemorrhaging
December 6, 6:11 PMLA Health Technology ExaminerVictoria Nicks
H1N1 vaccine ineffective against D225G mutation found in Utah
A sample from a Utah swine flu patient has been analyzed, and shows the same H1N1 mutation found in Ukraine and other locations around the world. This mutation of the pandemic A H1N1 swine flu virus, the receptor binding domain change of D225G, is associated with lung hemorrhaging and resistance to the swine flu vaccine.
H1N1 mutation: D225G
The H1N1 mutation that affects the receptor binding domain D225G causes the swine flu virus to attach to cells deep in the lungs. This can cause severe illness, including lung hemorrhaging. The D225G RBD has been found in cases of swine flu in Ukraine, Brazil, and other locations around the world. Symptoms of bleeding in the lungs have been identified here in the United States.
It’s possible that more cases exist, but the type of sample taken during testing may limit the number of cases identified. Swine flu samples are typically taken with a swab of the inside of the nasal passage, while the D225G strain would be found in lung tissue. The severity of H1N1 Influenza infections in Ukraine has been closely linked to the D225G RBD change, as well.
H275Y H1N1 influenza virus mutation
The H275Y H1N1 mutation causes the virus to be resistant to the antiviral medication Tamiflu. Currently, the H1N1 infections that are Tamiflu-resistant still respond to Relenza, another antiviral drug used to treat swine flu in the U.S. This mutation has been found in clusters in Maryland, North Carolina, and Wales, and in individual cases all over the world. In France, a combination of the H275Y mutation and the D225G mutation were found in a fatal case of the swine flu.
Reference:
Recombinomics
China offers aid to Ukraine to fight A/H1N1 flu
(Xinhua)
Updated: 2009-12-08 10:42
http://www.chinadaily.com.cn/china/2009-12/08/content_9138110.htm
KIEV: China will donate relief goods to Ukraine to help the country prevent the spread of A/H1N1 flu, according to an agreement signed here on Monday.
The 3.5-million-yuan (about $500,000) aid includes facemasks, latex gloves, medicine and medical equipment.
Zhou Li, Chinese ambassador to Ukraine, and Igor Yakovenko, deputy health minister of Ukraine, signed the agreement on behalf of their governments.
“China and Ukraine are friendly countries. We should support each other and the Chinese government is willing to offer necessary assistance to Ukraine at its difficult time,” Zhou Li said.
Yakovenko thanked the Chinese government for its timely assistance, saying that the aid from China would play an important role in helping Ukraine fight against the spread of the flu.
“China is one of the first countries that responded to our call for help with invaluable material and moral support,” said Yakovenko.
“The first wave of flu epidemic in Ukraine is over, but we should be ready for the outbreak of a second wave,” Yakovenko added.
Ukraine
08/Dec/09
3 new deaths, 472 in total
http://www.moz.gov.ua/ua/main/press/?docID=14299
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Ukraine Cases Spike - D225G and D225N Found
Recombinomics Commentary 23:55
December 8, 2009
2,187,836 Influenza .ARI
132,178 Hospitalized
472 Dead
The above numbers, from the Ukraine Ministry of Health represent a spike in cases yielding a daily increase of 86,578. The jump was widespread, but the biggest jumps were Donetsk increased 12,586 to 160,212 and Dnipropetrovsk which increased 9.813 to 149,358 (see map). This jump may be signaling a move into the real winter season.
Ukraine is under close scrutiny because sequences released by Mill Hill at GISAID had D225G in all four fatal cases and CDC sequences at GISAID identified D225N in new cases, which were also likely fatal, so all HA sequences from fatal cases in Ukraine have had a receptor binding domain change at position 225 (D changing to either G or N). Since the same changes had been seen previously in Sao Paulo, Brazil over the summer, and now cases were being identified in severe and fatal Scandinavian countries,
The finding D225G or D225N in all fatal cases in Ukraine clearly demonstrates that the changes are transmitting, comments from Scandinavian officials notwithstanding. More detail on the new patients and sequences would be useful.
http://www.recombinomics.com/News/12080902/Ukraine_472_D225N.html
Commentary
D225N in Ukraine Raises Pandemic Concerns
Recombinomics Commentary 00:05
December 9, 2009
New sequences from Ukraine have been placed on deposit at GISAID by the CDC. Although the sequences are partials, the receptor binding domain is covered in all 5 HA sequences. Three of the sequences have numbers and ages of patients which match three of the surviving patients tested by Mill Hill and these three sequences have a wild type receptor binding domain. However, the other two, A/Ukraine/01/2009 and A/Ukraine/02/2009 do not match ages on Mill Hill samples and are likely samples from two fatal cases. Both of these sequences have a receptor binding domain change at position 225, but both have D225N, while the Mill Hill sequences were D225G. Moreover, one of the D225N sequence is a mixture with the wild type sequence.
All sequences are the same sub-clade and collected within a day of each other. They are likely from six fatal cases, once again highlighting the significance of the receptor binding domain and arguing for transmission, since each change is in at least two samples and a change at position 225 is found in 100% of the fatal samples. Both of these changes had been identified in fatal lung infections in Sao Paulo, further linking recent changes (D225G and D225N) to severe and fatal cases.
More detail on the status of these patients and sample source would be useful, as would sequence data from multiple sites in the same patient.
However, it is increasingly clear that the receptor binding domain changes are transmitting and are associated with severe and fatal infections.
D225N in Ukraine
http://www.recombinomics.com/News/12090901/D225N_Ukraine.html
Ukraine
09/Dec/09
2 new deaths, 474 in total. 71 805 new cases.
http://www.moz.gov.ua/ua/main/press/?docID=14315
It sounds extremely serious. Thanks for the pings. On the radio today I heard a reporter mention that “they” don’t know if we will have a third wave here, and if we do whether it will be serious, but that we should prepare as though it will be much worse than the first 2 waves.
That makes sense about what he said about a 3rd wave .
I thought this new info was interesting .
North Korea says dozens have died of swine flu
http://www.latimes.com/news/nation-and-world/la-fg-north-korea-flu10-2009dec10,0,5668378.story
By John M. Glionna and Ju-min Park December 9, 2009
Reporting from Seoul - Reclusive North Korea today took the unusual step of acknowledging that it has suffered an outbreak of swine flu, with officials saying the virus has killed dozens of citizens.
The Public Health Ministry confirmed one outbreak in the city of Sinuiju on the Chinese border and a second in the capital city of Pyongyang, according to the official Korean Central News Agency.
“The relevant [agency] is further perfecting the quarantine system against the spread of this flu virus while properly carrying on the prevention and medical treatment,” the agency said.
Lee Seung-yong, general manager of Good Friends, estimated that 50 people have died since the flu broke out in November.
He called the acknowledgment by North Korea unusual.
“Usually, North Korea does not tell the outside world about its national disasters,” he said. The admission “is very unusual and the spreading flu is something that North Korea cannot hide.”
North Korea says dozens have died of swine flu
http://www.latimes.com/news/nation-and-world/la-fg-north-korea-flu10-2009dec10,0,5668378.story
By John M. Glionna and Ju-min Park December 9, 2009
Reporting from Seoul - Reclusive North Korea today took the unusual step of acknowledging that it has suffered an outbreak of swine flu, with officials saying the virus has killed dozens of citizens.
Confused.....
FYI, a very interesting post regarding an outbreak of H1N1 swine flu in North Korea.
Ducks.
Thank you both. Its not done yet.
I thought the same thing !
Why are they sharing the info with the rest of the world .....
Well... you know that there is serious starvation going on over there, but perhaps there actually are a few ducks that haven’t already been eaten.
Ukraine
10/Dec/09
5 new deaths, 479 in total.
69 017 new cases of ILI/flu, 2 328 658 in total.
http://www.moz.gov.ua/ua/main/press/?docID=14370
Commentary
D225G and D225N Diversity Confirmed in Fatal Utah Case
Recombinomics Commentary 22:22
December 11, 2009
http://www.recombinomics.com/News/12110903/D225G_D225N_Utah_Fatal_Conf.html
A 28-year-old Utah woman who died this summer of H1N1 swine flu had a mutated form of the novel virus.
The state routinely sends samples to the CDC for it to sequence to look for significant mutations — ones that would be resistant to the vaccine, for example.
That is not the case with the Utah mutation. Even if the mutated virus was passed from this woman to someone else, and there is no evidence it has, “the vaccine would still be protective,” Herlihy said.
“Mutations occur very regularly in influenza,” she said. “We are monitoring for genetic mutations of significance. We do not believe this is a genetic mutation of clinical significance.”
The above comments confirm that A/Utah/42/2009 with D225G and D225N was from a fatal (28F) cases. However, the additional comments regarding significance and effect on the vaccine are curious. The two receptor binding domain changes have been noted at increased frequencies since the summer and almost all cases are severe or fatal. In Sao Paulo, D225G was identified in two patients and D225N was in two others and all four were fatal. A case in China recovered after a month in the hospital and was described as the first severe cases in the Province. In Ukraine Mill Hill sequenced H1N1 from four fatal cases, and all four had D225G. The CDC sequenced two more, which were also likely to be from fatal cases, and both had D225N. The Ukraine data was followed by a review of samples in Norway and three patients with D225G were identified. Two were fatal and one severe. France also found two patients with D225G and both were fatal (and one also had H274Y).
The above confirmation extends the cases to the US and again involves a fatal case who was 28 and not said to have an underlying condition.
Although the CDC has placed these sequences on deposit, they have not released an antigenic characterization. Similarly, the two samples from Ukraine were said to be California/7-like based on PCR instead of neutralizing titer when tested against ferret reference sera.
Mill Hill tested one of the Ukraine sequences with D225G and classified it as a “low reactor” indicting the titer was at least four fold lower than the positive control, raising vaccine reactivity concerns. Thus, the basis for the statement that the vaccine would “be protective” is unclear.
Similarly, after the WHO called the changes in sequences from fatal cases in Ukraine insignificant, the finding of the changes in dead and severe cases in Norway led to a revision of the “not significant” statement.
In June and July there was a spike in Utah deaths. 10% of the US fatalities in that timeframe were from Utah. The presence of D225G and D225N in the above fatal case suggests that these changes were circulating in the area and may have contributed to the spike in fatalities.
Release of sequence data from samples collected at the site of infection, such as lung, would be useful.
Ukraine
14/Dec/09
4 new deaths, 501 in total.
83 137 new cases of ILI, 2 546 622 in total
http://www.moz.gov.ua/ua/main/press/?docID=14405
466 cases of pandemic H1N1 influenza confirmed by Ukrainian laboratories
http://en.for-ua.com/news/2009/12/15/104758.html
15 December 2009
The Ukrainian Health Ministry informed about 466 confirmed cases of pandemic H1N1 influenza.
Samples for an analysis have been taken from 2,494 people, including from the dead - 395, according to the methods recommended by the World Health Organization (WHO). As of Monday evening, the flu and ARI epidemic threshold was exceeded in 11 regions of the country.
As of December 14 evening, the flu and ARVI epidemic threshold was exceeded in 11 regions of the country.
Ukraine
15/Dec/09
6 new deaths, 507 in total.
143 941 (!!!!!!!!!) new ILI cases today, 2 690 563 in total
http://www.moz.gov.ua/ua/main/press/?docID=14423
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