Influenza Surveillance: 2014?-2015 H1N1 ?Swine?-Derived Influenza Viruses from India

[Ronan Kelly]

Influenza Surveillance: 2014?2015 H1N1 ?Swine?-Derived Influenza Viruses from India
Kannan Tharakaraman, Ram Sasisekharan
DOI: http://dx.doi.org/10.1016/j.chom.2015.02.019

Summary
The 2014-15 H1N1 outbreak in India has reportedly led to 800 fatalities. The reported influenza hemagglutinin sequences from India indicate that these viruses contain amino acid changes linked to enhanced virulence and are potentially antigenically distinct from the current vaccine containing 2009 (Cal0709) H1N1 viral hemagglutinin.

? 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

Full paper available here:

http://www.cell.com/cell-host-microbe/abstract/S1931-3128(15)00076-1

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Although there are limited Indian-origin influenza sequences available in the public database to make any causal inference on the perceived increased fatalities in India, examination of the 2014 Indian H1N1 HA sequences shows traits with potential cause for concern. Amino acid changes in specific positions in the receptor binding site (RBS) of 2009pdmH1N1 have been shown to impact glycan RBS specificity and have been linked to increased virulence and disease severity. Among these changes, the Indian-origin strain A/India/6427/2014 contains amino acid changes T200A and D225N compared to the 2009pdmH1N1 pandemic strain. The T200A amino acid change has been shown to improve human glycan receptor-binding of 2009pdmH1N1 HA (Xu et al., 2012b). The D225N mutation has been linked to increased virulence and disease severity in patients infected by the 2009 pdm virus (Ruggiero et al., 2013). Importantly, a previous study showed that the D225N mutation in the context of H1 HA affected receptor binding and also decreased susceptibility to NA inhibitors (McKimm-Breschkin et al., 2013). It should be noted that the D225N mutation was previously linked to serious illness resulting in hospitalization or death (L?vov et al., 2010). The high population density in India, ease of person-to-person transmission, and lack of effective treatment options create ample opportunities for this variant to sustain and become dominant. It is unknown if the strain A/India/6427/2014 is still in circulation; however, the apparent severity of the current outbreak seems to suggest that it could be.
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[Ronan Kelly]

NIV claims swine flu virus has not mutated, to submit report to Centre
Priyanka Vora, Hindustan Times, Mumbai| Updated: Mar 13, 2015 00:43 IST

The National Institute of Virology (NIV), Pune, debunked the findings of the international study that stated that the H1N1 virus in circulation in India has mutated. According to NIV officials, the strain analysed in the said publication and the sequence data of the original H1N1 virus was available with them, and it has not mutated.

In a press release, the NIV said the strain mentioned in the report of 2014 has no relevance to the current outbreak. ?Recently, NIV has analysed six full genome, which also suggest absent of mutation,? it said.

The premier institute has, however, been asked to submit a detailed report to the Union health and family welfare ministry about the study conducted by the MIT.
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http://www.hindustantimes.com/mumbai/niv-claims-swine-flu-virus-has-not-mutated-to-submit-report-to-centre/article1-1325751.aspx

[Ronan Kelly]

PRESS NOTE

From National Institute of Virology (NIV), Pune

Certain media inquiries have been received by National Institute of Virology, Pune, seeking information on possible mutations of Influenza A H1N1 virus circulating in India.

A publication in Cell Host & Microbe, 17, March 11, 2015 Elsevier Inc. [Page 279-282], entitled ?Influenza surveillance: 2014-2015 H1N1 ?Swine?-Derived Influenza Viruses from India? has been cited. Our experts have carefully examined the findings mentioned in the above-mentioned publication. We found that the strain analyzed in the said publication and the sequence data of the original H1N1 virus A/India/6427/2014 as available with NIV did not show any of these mutations. Subsequent report on antigenic/genetic analysis of this H1N1 virus by CDC/WHO as communicated to NIV also did not report any oseltamivir resistance or any other genetic changes in HA genes that could be virulent markers. The virus was similar to A/North Carolina/04-2014. The genetic analysis of the HA gene of the H1N1 isolates from the present 2015 outbreak do not show any such mutations as mentioned in the above publication.

Moreover, the strain mentioned in the report of 2014 has no relevance to the current outbreak of 2015. Recently NIV has analyzed six full genomes, which also suggests absence of such mutations.

This press release has been issued so that public has the correct information and does not get confused with the incorrect conclusion published in the above said publication.

*****

(Release ID :116939)

http://pib.nic.in/newsite/erelease.aspx?relid=116939

[Ronan Kelly]

Go read this whole article & follow up on some of the embedded links. Very odd. - Ro

Hello? Anyone seen my swine flu mutation?
Grist MediaBy Deepika Sarma | Grist Media ? 20 hours ago

An MIT study says the swine flu sweeping India might be a deadly new mutation. The National Institute of Virology in Pune firmly disputes this. How can there be such a vast difference of opinion? Could both be right or both be wrong? Is there a scientific conspiracy, a cover up, a screw up or something else entirely? We sought an independent scientific analysis and, as the Internet phrase goes, our conclusions may surprise you.
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When we asked Habermann, she ran the data independently and in her analysis of the sequences, she did find all three mutations in the March strain. In the May strain, she found just the first two. But given that no sequence from the current outbreak of 2014-15 is available, she points out, it cannot be discerned whether the current strain carries any of these mutations.

Now we have three possible explanations.
One: that the MIT researchers are right about the mutations (which Habermann’s analysis of the data confirms). The facts seem clear: the HA sequence from March 2014 deposited with the GISAID database does indicate the mutation. But whether this mutation exists in the current circulating strain in India, and the impact it has, can only be proven by examining the current strain itself and sufficiently monitoring the situation. This is why the joint study by NIV and NCDC referred to in the media is important.

Two: that the NIV is also right. It is possible that the NIV hasn’t found the three mutations indicated by the MIT researchers and Habermann if there is a discrepancy between the original data with the NIV and the data finally deposited with GISAID – something the NIV appears to hint at in its press release, which talks of “sequence data of the original H1N1 virus A/India/6427/2014 as available with NIV.” DT Mourya, the institute’s director, also appears to have indicated this discrepancy to a reporter. A slip, as it were, ’twixt cup and lip.

Three: That the NIV has not examined the data carefully enough, or is attempting to downplay the situation and maintain calm by denying the mutations. If the “original” data with the NIV does show mutations in the March 2014 strain, the NIV has either made an error or deliberately misled the public about their existence. Even if the mutations do not have a significant impact on the ground, that doesn’t explain why the NIV should entirely deny their presence.

Without more information from the NIV, it’s hard to figure out which of these scenarios – or which combination of them – is most likely. The NIV may be right about the 2014 D225N mutation being irrelevant to this year’s strain, whether or not it exists. And it may just be changes in the weather that have resulted in swine flu’s continued circulation. As for the rest, we’ll just have to wait and see. The entire mutations controversy has underlined, at the very least, the glaring holes that remain in the way India tracks and responds to influenza outbreaks.
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https://in.news.yahoo.com/hello--any...104901301.html

[Ronan Kelly]

The Mystery of the Missing Swine Flu Mutation
Be Deepika Sarma
Hours after the story on the swine flu mutations from 2014 (Hello? Anyone seen my swine flu mutation?) that India?s National Institute of Virology and two MIT researchers disagreed over was published, I received an email from the Press Office of the Centers for Disease Control and Prevention (CDC) Influenza division, which monitors swine flu globally, in response to my questions about the presence of the mutations.
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Here?s what the CDC says: that the H1N1 strain in question (collected in March 2014) did show the three mutations that the MIT researchers spotted, but it appears no more virulent than other H1N1 viruses circulating globally, and shows no decrease in susceptibility to drugs. It says that the D225N mutation, which the MIT researchers flagged as being potentially deadly, has been previously spotted in cases of H1N1 ranging from mild to severe. H1N1 viruses with this mutation have not been known to spread to other people, so the public significance of the mutation is unclear. The virus circulating worldwide has changed very little since it first emerged in 2009.
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http://thegrist.tumblr.com/post/115367231961/the-mystery-of-the-missing-swine-flu-mutation