Commentary
Worldwide Transmission of D225G
Recombinomics Commentary 06:45
November 27, 2009
http://www.recombinomics.com/News/11270901/D225G_WWT.html
The recently released sequences from patients in Ukraine provided valuable insight into the pathogenicity of H1N1 and the genetic change associated with the total destruction of both lungs in fatal cases. The description of the patients and the spread of receptor binding domain change, D225G, to multiple genetic bakgrounds via recombination led to the prediction that D225G would be found in the lung samples from fatal cases. The release of the sequences by Mill Hill confirmed the prediction. Sequences from 10 isolates were released and all four fatal cases had D225G. Moreover, all 9 cases from western Ukraine, which were from three Oblasts (Ternipol, Lviv, and Khmelnitsy) were from the same sub-clade as the fatal cases, but the samples from the upper respiratory tract did not have D225G. The absence of D225G from the upper respiratory tract is not a surprise because the specificity of D225G included alpha 2,3 receptors which are present in the lungs. Thus, the sub-clade with D225G can expand and cause a cytokine storm which destroys the lungs. Moreover, sequences with D225G have been designated as low reactors by Mill Hill, raising concern that immune responses and vaccine will select for D225G.
Although D225G transmits from patient to patient, only the samples from the fatal cases, which were from lung and throat samples were positive for D225G. The sequences from Ukraine led other countries to more fully investigate samples. Norway, which had seen an increase in fatalities announced the detection of D225G in two fatal and one severe case. Although those sequences have not been released, 25 HA sequences were subsequently released and one sequence had D225G as a mixture, confirming the mixed nature of samples with D225G.
Moreover, the sequence with D225G was the same sub-clade as Ukraine, and several matching sub-clades were in subsequent samples, but those samples did not contain D225G, again pointing to a requirement for sampling of appropriate tissues.
The implication of this sub-clade in the increase in deaths in Norway was the finding that the first fatality was also linked to the same sub-clade. The patient, 43F, was in previously good health and given a prescription for Tamiflu after visiting the hospital. However, she was sent home and died two days later. This type of rapid death had been noted for many of the Ukraine cases. Full sequences were generated confirming that the NA sequence was closely related to the NA sequences from western Ukraine, but the sample was from the trachea and did not have the D225G. However, the association of this sub-clade with the first patients death and the finding of D225G in the first isolate matching this sub-clade support D225G transmission as a mixture, with detection in appropriate sampling of the lower respiratory tract.
Phylogenetic analysis of public sequences indicate that the Norway/Ukraine is widespread, strong suggesting that D225G has sread worldwide. However, detection of D225G, as was seen in Ukraine requires that the proper samples are tested.
The finding of D225G in four of four fatal cases in Ukraine leaves little doubt that the polymorphism is transmitting and the recent classification of Ukraine sequences wirg D225G suggests the spread will accelerate. The finding of the same change in unlinked patients in two Oblasts in western Ukraine is similar to the finding of swine H1N1 in two counties in southern California in April. The fact that the two California cases had no link to swine or each other, and were collected from patients over 100 miles apart conclusively demonstrated that the swine H1N1 was efficiently transmitted human-to-human and many more cases would be identified.
The data from Ukraine conclusively demonstrate that D225G is efficiently transmitting and the transmission traces back to earlier isolates from Norway of the same sub-clade with D225G.
Since D225G is frequently not detected in samples from the upper respiratory tract, another method of tracking is through phylogenetic analysis, which shows that the Norway/Ukraine sub-clade is widespread, even though all HA sequences do not have D225G, as was seen in Ukraine.
The worldwide transmission of the Norway/Ukraine sub-clade, or other sub-clades with D225G raises concerns that associate hospitalizations and fatalities will have a significant uptick as an increasing number of patients get exposed to this sub-clade linked to D225G.
More surveillance of low respiratory tract infections would be useful.
Ukraine
Knyazevich: There is no guarantee that tomorrow Ukrainian will not die because they do not have vaccination
27/Nov/09
Health Minister Vasily Knyazevich not exclude the possibility of failure of the vaccination campaign against influenza A/H1N1 in connection with mistrust of the population and discrediting of such preventive measures after the case of the death of student from Kramatorsk.
He said in an interview with Government courier.
“Such threats (failure of the vaccination campaign) are real. After the campaign we have problems even with mandatory vaccines, not to mention the voluntary, were not very popular among our citizens ... today all afraid outbreak of influenza, but no guarantee that Ukrainian tomorrow will not only die from infections that were exposed antyvaktsynalnykiv “- Kniazevych said.
Commenting on the situation of unplanned (optional) immunization against measles and rubella Knyazevich said that her top was still scheduled for autumn 2007. “... Health of Ukraine confirmed its readiness to host the 2007 campaign, additional immunization and consented to the importation and use of 9 million doses of vaccine (measles and rubella vaccine production of the Indian Institute of sera) without its registration as a humanitarian aid that meets current legislation, - he informed, adding that the quality of the vaccine by the WHO Prequalification guaranteed.
However, according to the minister, an order was signed in 2007. Instead, signed an order approving a plan additional immunization against measles and rubella in 2008.
Knyazevich once again assured that the death of a schoolboy Anton Tishchenko Kramatorska not associated with the vaccine or vaccination.
Head of the Ukrainian Ministry of Health also commented on the response of WHO and UNICEF for the decision on the impossibility of use in Ukraine in 2009, measles and rubella, given as humanitarian aid. In particular, he recalled that previously the Minister of Economy and Finance, Gordon Brown has put much effort to persuade international donors to provide funds Ukraine to campaign for additional immunization, while dozens of countries much poorer than the Ukrainian state, also expected the vaccine.
“I’m hard to say whether WHO will go toward Ukraine as it was before, and to provide free vaccine. While we stand in line for flu vaccine from California, as hundreds of other countries. To date only two countries (Russia and Canada ) provided us with materials for early registration of influenza vaccines, “- said Knyazevich.
According to the minister, an additional vaccination against measles and rubella in 2009 will, according to predictions of epidemiologists, can lead to outbreaks of measles and rubella in 2010-2011.
As reported, the Cabinet of Ministers of Ukraine approved a plan to target the population against influenza for the 2009-2010 and created a coordinating council to reform the health system.
Experts from the World Health Organization investigation found no causal connection between the death of a schoolboy with his Kramatorska vaccination.
http://ua.korrespondent.net/tech/1021919