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Sequence analysis without sequences

http://www.recombinomics.com/News/11141 ... lysis.html

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Swine trH3N2 Phylogenetic Analysis Without Sequences
Recombinomics Commentary 03:14
November 14, 2010


The viruses identified in Pennsylvania and Wisconsin are similar to viruses that infected a patient in Iowa in September 2009, a patient in Kansas in August 2009 and a patient in Minnesota in May 2010.

The above comments are from the CDC update describing the two most recent swine trH3N2 cases. The “similar” characterization is not very informative. The CDC released sequences from the Kansas infection, but have withheld the sequences from the other cases...........

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Commentary

http://www.recombinomics.com/News/11291 ... uzzle.html

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Conclusions and recommendations
Following recent infections in children in North America with a swine-origin triple reassortant influenza A(H3N2) virus that includes a genetic component from the pandemic 2009 virus, and with probable human-to-human transmission of these viruses, ECDC has come to the following preliminary opinion:
• These viruses are known to be found in pigs in North America but they have not been found in pigs in Europe (EU/EEA countries). However, surveillance for influenza in pigs is weak in both North America and Europe, and surveillance for infections in humans in close contact with pigs is notably weak in Europe. Hence all such statements on the epidemiology of swine influenzas must be treated with caution.
• Most of the US cases experienced only mild disease. Those hospitalised had underlying conditions and all patients recovered completely.
• These viruses are susceptible to the neuraminidase inhibitors (oseltamivir and zanamivir) though the current A(H3N2) component of seasonal influenza vaccines is unlikely to provide protection. Older people are likely to have some protection from exposure to earlier vaccines.
• It is considered by the United States Centers for Disease Control (CDC) that there had already been some very limited human-to-human transmission of these and similar viruses in the US.
• Unlike in March 2009 (the start of the pandemic) there are no reports of numbers of unexplained influenza infections elsewhere in the Americas. Hence it is unlikely that these US cases represent outliers for a larger phenomenon.
• Overall, therefore, the immediate direct threat to human health in Europe is low.
• ECDC staff are following the situation closely and are in direct contact with the WHO, the US CDC and relevant experts in EU Member States.
• There is a need to ensure that these infections could be detected through diagnostic testing in European national influenza laboratories.
• There are strong public health arguments for more active virological surveillance of pig herds in Europe (and North America) including active surveillance of infections in humans that are in direct or indirect contact with pigs.
• Equally justified are more formal approaches to assessing emerging influenza viruses for their pandemic potential and such virological risk assessments should continue to be developed.
• Unusual influenza viruses should continue to be referred to National Influenza Centres and on to the WHO Collaborating Centre in Europe, along with relevant clinical and epidemiological data.

http://www.ecdc.europa.eu/en/publicatio ... merica.pdf

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More nonsense on "swine exposure" signal a serious ECDC failure to analyze scientific data, especially sequences.

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CONSULTED EXPERTS
Martin Beer, Friedrich Loeffler Institute, Germany
Joseph Bresee, Centers for Disease Control and Prevention, USA
Bruno Lina, National Influenza Centre, University of Lyon, France
John McCauley, WHO Collaborating Centre, UK
Marianne van der Sande, RIVM, Centre for Infectious Disease Control, the Netherlands
Sylvie van der Werf, Institute Pasteur, Paris, France
Kristien Van Reeth, University of Gent, Belgium
In consultation with the World Health Organization

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Laboratory diagnosis
Diagnostic RT-PCR for generic influenza A virus will detect these viruses as human influenza A. However, the subtype-specific RT-PCR for either H3 or N2 of human influenza A viruses will most probably have a decreased sensitivity or will result in no detection of the SO-A(H3N2) viruses. Probes directed against other genes, e.g. the nucleoprotein gene as was used during the early phase of the 2009 pandemic caused by the A(H1N1)pdm09 virus, will enable preliminary differentiation between human seasonal H3N2 viruses and these zoonotic H3N2 viruses. Therefore, swine-origin specific subtype RT-PCR, antigenic characterisation, and partial or full genome sequencing are the most appropriate techniques to distinguish between the human and these new zoonotic origin influenza viruses. The European influenza reference laboratories (National Influenza Centres) are aware of the detection challenges and a number are updating their detection protocols to be able to make this distinction. However, it is not clear what the strategies are across national laboratories in the EU/EEA countries
The National Influenza Centres in France and the WHO Collaborating Centres in Atlanta, US and London, UK have been analysing the genetic sequences on these viruses. They essentially agree that it is very likely that the current seasonal vaccine would not protect against infection should these viruses appear in humans in Europe. However, the phylogenetic analysis of these viruses also suggests that those infected or vaccinated in the past with strains with antigenic characteristics similar to the strain (H3N2) may have some degree of protection against this virus. This possible cross-protection could be verified by sero-epidemiological surveys to assess the prevalence of antibodies’ cross-reactive potential protection by age group [18]. This observation is consistent with the notably young ages of many of the cases in the United States [3–4].

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Human public health importance of swine influenza
The public health importance of swine influenza is twofold. Firstly there is the direct risk of infection for those coming into close contact with pigs or through limited human-to-human transmission. Triple reassortant swine influenza viruses with avian, human and swine genes have been circulating in pigs in the US, and have been transmitted to humans. This is now also the case for the triple reassortant viruses with the additional A(H1N1) M-gene [1]. However, none of these reassortant viruses has been able to maintain themselves in the human population and, in addition, there have been no large clusters of infection. The second risk is of reassortment to produce a novel virus (possibly a strain with pandemic potential), either in the pig or in the human host, by co-infection with a human and a swine strain. The pandemic A(H1N1)pdm09 influenza virus is so far the only swine-origin virus that has shown the capacity to spread readily and extensively between humans. However, it demonstrates that this is a possibility.

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Clearly, the assessors don't have a clue about teh significance of the SAME H3N2pdm11 in humans and ABSENCE in swine. Their analysis is FATALLY FLAWED.

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ECDC RAPID RISK ASSESSMENT FOR THE EU
It is important to emphasise that the viruses circulating in pigs in North America seem to be quite different from those reported in pigs in Europe. Swine influenza A(H3N2) viruses predominate in North America as triple reassortant viruses while the H3N2 viruses that are endemic in swine in some regions of Europe are antigenically and genetically different [6,7]. Reports of swine-origin viruses in humans in North America occur most years and since ‘novel influenza A viruses’ are a nationally notifiable disease in the US, laboratories that detect a possible novel influenza A virus are required to investigate the case and rapidly send laboratory specimens to the CDC for testing [2]. By contrast, reports of swine viruses in humans in Europe are rare: there have been only two published reports since 2008 (one in Spain and one in Germany) plus the three cases from Switzerland that have yet to appear in the literature [14–16].
However, it must be noted that the discovery of the Spanish and German cases in humans was almost accidental, so it is likely that the numbers of human infections are underestimated. Following the emergence of the 2009 pandemic from pigs in Mexico there is a strong public health case for increased active ascertainment of human infections with swine viruses in Europe [15]. Finally it should be noted that human influenza viruses from the 2009 pandemic may be circulating in pig herds in Europe, giving rise to the possibility of reassortment as demonstrated recently in Germany in which case these infections may not be detectable by conventional testing [10].
The risk of the emergence of a pandemic virus based on the American triple reassortant swine viruses with or without the A(H1N1) M gene cannot be known. This is only one of a number of potential pandemic influenza viruses. Others include A(H9), A(H2) and A(H5N1) viruses. An international initiative recently started with the aim of judging which candidate viruses are most likely to warrant the development of pandemic preparedness tool-kits that include both diagnostic components and early vaccine development [19]. That initiative is not yet developed enough to justify its application to S-OtrH3N2 viruses but they would be early candidates for consideration. In Europe this initiative is being supported by the European Food safety Authority [20].
CONCLUSIONS AND RECOMMENDATIONS
The viruses in question have not been seen in pigs in Europe (EU/EEA) but there has been swine-to-human transmission in Europe with European viruses. However, there are no reports of anything but mild self-limiting illness and no ongoing transmission. The clinical picture is in stark contrast to avian influenza A(H5N1) infections [11].
Surveillance for infections in humans in contact with pigs is not as robust in Europe as in the US and there are strong public health reasons for strengthening surveillance of animal infections on both continents. Human influenza viruses from the A(H1N1) pandemic may be circulating in pigs and reassortant viruses from pigs have also been described recently. This is in addition to integrated virological, clinical and epidemiological surveillance of human infections in various healthcare settings (community, primary care, hospitals including intensive care units).
It is important to ensure that there is at least national capacity for detecting these viruses in EU/EEA countries and ECDC should work with the Community Network of Reference Laboratories (CNRL) to determine what methods are being used. Depending on the results of that exercise it may be worthwhile to issue guidance on recommended options for potential sampling and testing.
Another area requiring rapid work is determining what to call these and other new influenza viruses, since whilst a virological terminology such as S-OtrA(H3N2) plus an A(H1N1) M gene and A(H1N1)pdm09 may be essential for technical discussions, it does not facilitate communication.
It is impossible to comment on the pandemic potential of the current swine influenza viruses but formal virological risk assessments on the pandemic potential of emerging viruses like these are under development.
It is possible that these triple reassortant infections will appear in Europe, particularly if there is more human-to-human transmission, which could lead to imported cases. Hence Member States should continue to work with WHO and ECDC-CNRL to ensure there is diagnostic capacity at least at the national level in EU/EEA countries.
Finally, the situation highlights the importance of early and rapid referral of unusual influenza viruses, along with relevant clinical and epidemiological data, to National Influenza Centres and on to the WHO Collaborating Centre in Europe.
Relevant EU swine influenza websites:
ESNIP2 - European Surveillance Network for Influenza in Pigs 2: http://www.esnip.ugent.be/ ESNIP3 - European Surveillance Network for Influenza in Pigs 3: http://www.esnip3.eu/ FLUPIG - Pathogenesis and transmission of influenza in pigs: http://www.flupig.ugent.be/
CONTACT: support@ecdc.europa.eu
RISK ASSESSMENT Swine-origin triple reassortant influenza A(H3N2) viruses in North America
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References
1. Centers for Disease Prevention and Control Swine-Origin Influenza A (H3N2) Virus Infection in Two Children --- Indiana and Pennsylvania, July--August 2011 CDC Morbidity and Mortality Weekly Report, September 9, 2011 / 60(35); 1213-1215
2. Centers for Disease Control and Prevention (CDC) Reported human Infections with Swine Origin Influenza Viruses (SOIV) in the United States since 2005 November 22nd 2011 http://www.cdc.gov/flu/swineflu/soiv_cases.html
3. Centers for Disease Control and Prevention November 22nd 2011 Iowa Reports Novel Influenza Infections in Three Children http://www.cdc.gov/media/haveyouheard/s ... uenza.html
4. Centers for Disease Control and Prevention (CDC) Limited Human-to-Human Transmission of Novel Influenza A (H3N2) Virus — Iowa, November 2011 MMWR November 23, 2011 / 60(Dispatch);1-3 http://www.cdc.gov/mmwr/preview/mmwrhtm ... 0d1123a1_e
5. WHO Influenza like illness in the United States of America November 24th 2011 http://www.who.int/csr/don/2011_11_24/en/index.html
6. WHO Report of the Review Committee on the Functioning of the International Health Regulations (2005) and on Pandemic Influenza A (H1N1) 2009 (Fineberg Report) Final submitted to the World Health Assembly 2011 http://apps.who.int/gb/ebwha/pdf_files/ ... _10-en.pdf
7. Kyriakis C.S., Brown I.H., Foni E., Kuntz-Simon G., Maldonado J., Madec F., Essen S.C., Chiapponi C., Van Reeth K. - Virological Surveillance and Preliminary Antigenic Characterization of Influenza Viruses in Pigs in Five European Countries from 2006 to 2008. Zoonoses Public Health, 2011: 58, 93-101.
8. Olsen CW, Brown I, Easterday BC, Van Reeth K. Swine influenza. In: Straw B.E., Zimmerman J.J., D’ Allaire S., Taylor D.J., eds. Diseases of Swine, 9th edition, Iowa State University Press, Ames, Iowa, 2006: 469-82.
9. Van Reeth K, Brown IH, Dürrwald R, Foni E, Labarque G, Lenihan P, et al. Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002–2003. Influenza and other respiratory viruses. 2008;2(3):99-105.
10. Starick E, Lange E, Fereifuni S, Bunzenthal C, Hoveler R, Kuczka A et al. Reassorted pandemic (H1N1) 2009 influenza A virus discovered from pigs in Germany. J Gen Virol 2011; 92: 1184-8.
11. Van Reeth K. Avian and swine influenza viruses: our current understanding of the zoonotic risk. Vet Res. 2007;38(2):243-60.
12. Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a review of the literature. Clin Infect Dis. 2007;44(8):1084-8.
13. Neustadt RE, Fineberg HV. The swine flu affair: decision making on a slippery disease. Washington: US Department of Health, Education and Welfare 1978
14. Adiego Sancho B, Omeñaca Terés M, Martínez Cuenca S, Rodrigo Val P, Sánchez Villanueva P, Casas I, Pozo F, Pérez Breña P. Human case of swine influenza A (H1N1), Aragon, Spain, November 2008. Euro Surveill. 2009;14(7):pii=19120. Available online: http://www.eurosurveillance.org/ViewArt ... leId=19120
15. Van Reeth K, Nicoll A. A human case of swine influenza virus infection in Europe – implications for human health and research. EuroSurveill. 2009;14(7):pii=19124. Available from: http://www.eurosurveillance.org/ViewArt ... leId=19124
16. ECDC Public Health Development. True swine influenza in humans: recent different findings in the United States and Europe (Germany). 28 October 2011.
17. Gerloff NA, Kremer JR, Charpentier E, Sausy A, Olinger CM, Weicherding P, et al. Swine influenza virus antibodies in humans, western Europe, 2009. Emerg Infect Dis [serial on the Internet]. 2011 Mar [date cited]. http://dx.doi.org/10.3201/eid1703100581
18. CDC. Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza Mmwr. 2009 May 22;58(19):521-4.
19. WHO Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness and Standardization of terminology of the pandemic A(H1N1)
RISK ASSESSMENT Swine-origin triple reassortant influenza A(H3N2) viruses in North America
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2009 virus Weekly Epidemiological Record 21 October 2011, vol. 86, 43 (pp 469–480)
http://www.who.int/wer/2011/wer8643.pdf
20. ECDC. Public Health Development. Virological Risk Assessment of Pandemic Potential - EFSA Call for proposals18th July 2011. Available at: http://ecdc.europa.eu/en/activities/sci ... 30&ID=1156

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