Thursday 12 June 2008
Public Health Developments
Meetings and workshops
Request for Contributions
Seasonal Influenza – European Status
Text updated from: European Influenza Surveillance Scheme (EISS) Weekly Electronic Bulletin
The next EISS update for weeks 24-25 will be published on 27 June 2008
Issue 265, Week 23 (02/06/2008-08/06/2008)
Sporadic laboratory confirmed cases of influenza in Europe in recent weeks
Summary: Seasonal influenza activity in Europe has now come to and end and the number of laboratory confirmed cases of influenza is now very low (18 in the past two weeks). Ten countries reported an assessment of the geographical spread of influenza activity in week 23/2008: England reported sporadic activity and nine countries reported no influenza activity.
In week 22/2008 and 23/2008, there were a total of 18 influenza virus detections in Europe (see graph and table for further details): in England (6), Hungary (1), Ireland (1), Norway (6) and Slovakia (4). All detections were reported from non-sentinel sources, i.e. detected through the routine activities of diagnostic laboratories. There were 16 (89%) detections of influenza B virus and two (11%) of influenza A virus (not subtyped).
During the 2007-2008 season influenza A was dominant in the first half of the season and influenza B was dominant towards the end of the season (as of week 09/2008) [click here]. In the month of May 2008 (defined as week 19-22/2008), influenza B remained the dominant virus type with 156 detections (87%). However, whereas influenza A(H1N1) was clearly the predominant influenza A subtype during the 2007-2008 season (97% of subtyped A viruses), the subtype A(H1) and A(H3) were detected at the same levels in May (two detections of each along with 19 A un-subtyped viruses).
There have been no reports of unusual influenza activity in Europe at a community level (i.e. in a region or local area such as a city, county or district) since week 16/2008.
Background: The Inter-season Electronic Bulletin presents and comments influenza activity based on virological data reported to EISS. The Inter-season Electronic Bulletin will be published between week 21/2008 and week 39/2008.
The spread of influenza virus strains and their epidemiological impact in Europe are being monitored by EISS in collaboration with the WHO Collaborating Centre in London (United Kingdom) and the European Centre for Disease Prevention and Control in Stockholm (Sweden).
Other bulletins: To view national/regional bulletins in Europe and other bulletins from around the world, please click here.
Full interactive EISS bulletin including maps and graphs by country and informative links in the text
National/regional bulletins in Europe and other bulletins from around the world
Links to general information from EISS:
General information on EISS, including background, membership and information on citing the EISS bulletin
Definitions of epidemiological indicators used by EISS
Seasonal Influenza – European Status - Oseltamivir Resistance
Resistance to oseltamivir (Tamiflu) in some European influenza virus samples
As the influenza season is over, all data on the WHO, ECDC and EISS web-sites will now be updated only monthly with the next update at the end of June. Data can be expected to change because of testing of specimens taken earlier in the season
Updated 28th May 2008 – next update at the end of June
In late January 2008, antiviral drug susceptibility surveillance of seasonal influenza viruses in Europe (the EU-EEA-EFTA countries) by the EU-funded VIRGIL network and National Influenza Centres revealed that some of the A (H1N1) viruses circulating this season (winter 2007-8) were resistant to the antiviral drug, oseltamivir through mutation at position 274 in the viral neuraminidase gene. Analysis of 2748 A(H1N1) viruses from 24 European (European Union, EEA/EFTA) countries isolated between November 2007 and late May (data archived on May 28th) showed that 680 were resistant to oseltamivir, but retained sensitivity to zanamivir and amantadine. The data are shown as a figure with a linked table.
It should be noted that the influenza season has now finished in Europe so that new detections like this and other changes in the totals are the result of testing of specimens from during the season and checking of data for example to eliminate duplicates.
The proportion of A(H1N1) viruses that are oseltamivir resistant varied significantly across Europe. The highest proportion of resistant viruses to date have been in Norway where 182 (67%) of the 270 samples are resistant to oseltamivir, whereas no resistant viruses have been detected in five of the 24 countries.
Surveillance in previous years by the Virgil Project found <1% of circulating viruses to be resistant The predominant influenza A viruses in Europe in winter 07/08 were A(H1N1) viruses, antigenically similar to the A/Solomon Islands/3/2006 virus included in the 2007/08 N Hemisphere vaccine. As the season progressed influenza B viruses started to circulate and then predominated. There were only limited circulation of other influenza A in Europe. Further details on country to country virus distribution this season are available on the European Influenza Surveillance Scheme (EISS) weekly update which were also summarised in ECDC’s Influenza News.
Following the observation of a high level of resistance to oseltamivir in the A(H1N1) viruses circulating in Norway, the Norwegian authorities notified their EU partners and the World Health Organization (WHO) of this situation at the end of January. The Norwegian Public Health Institute also published an advisory to doctors and the public. The country with the second highest proportion has been France with 231 (47%) of 496 specimens showing the marker for oseltamivir resistance. This was followed by the Netherlands and Luxembourg with proportions of 30% and 26% respectively. There is no evidence that the appearance of these new viruses are related to use of oseltamivir which is currently seemingly not widely prescribed in most European countries. ECDC is now working with the manufacturer and national authorities to gather more information on routine oseltamivir use in Europe.
Experts from the European Centre for Disease Prevention and Control (ECDC), the European Commission, the European Influenza Surveillance Scheme and the World Health Organization (WHO) are currently assessing the significance of the data from the EISS VIRGIL network. An interim European risk assessment has been published by ECDC and comments on this are welcomed to email@example.com. Global surveillance has started coordinated by WHO and has this has found evidence of similarly resistant viruses in North America and the Far East. All data including that on the WHO web-site are updated every Thursday at present.
Although sporadic low level transmission of drug resistant viruses may have taken place since 1999 when the Neuraminidase Inhibitor drugs first were licensed, the 07/08 winter season is the first time there has been widespread and sustained transmission of such viruses in the community. Similar viruses have been seen before, but usually following treatment. Such viruses previously have not been able to readily transmit and have rapidly disappeared. Clinical experience in Norway suggests that people who become ill with an oseltamivir resistant strain of A(H1N1) have a similar spectrum of illness to those infected with “normal” seasonal influenza A which can cause severe disease or death in vulnerable people (older people, those with debilitating illnesses and the very young). This is now being investigated in national and international studies coordinated by ECDC.
At this stage the significance of these findings remains uncertain. The emergence of drug resistance in the context of limited drug use is unexpected, and the extent of future circulation is difficult to predict. ECDC, WHO, EISS, VIRGIL and authorities in the member states are undertaking intensive surveillance and progress will be reported through this and other relevant web-pages. A summary of the arrangements for the EU EEA & EFTA Countries is on the ECDC web-site this is also available in a pdf version as a briefing for policy makers in the EU and EEA/EFTA Member States
For information on seasonal influenza and how to protect yourself against it.
Data were provided by the European Influenza Surveillance Scheme http://www.eiss.org/index.cgi and the VIRGIL Project http://www.virgil-net.org/ ECDC would like to thank all countries, virologists, clinicians and others for contributing data. Funding for the VIRGIL project comes from the European Union FP6 Research Programme
Information on Antivirals and Antiviral Resistance
There are fluctuating reports in the media of influenza A(H5N1) and other avian influenza infections in birds and humans. ECDC monitors these carefully as part of its epidemic intelligence work. However without laboratory confirmation ECDC only rarely mentions these media reports in this output.
AVIAN INFLUENZA – HUMAN HEALTH - INDONESIA
No human cases of A(H5N1) have been officially reported by WHO since 28th May. However, the Indonesia Government has reported an unconfirmed further fatality, a 15-year-old girl from Southern Jakarta, who died of A(H5N1) last month. If confirmed, this would be Indonesia's 109th fatality and 134th case.
In a new development there are media reports that the Indonesian Minster of Health has decided to withhold immediately notifying WHO and the global influenza community of every human case of H5N1, but instead has made a commitment to produce updated information on cases at regular, but unspecified intervals.
CDC news: Indonesia To Keep Quiet On Bird Flu Deaths After 15-Year-Old Girl Dies, Health Minister Says It Will Not Announce Future Fatalities. (http://www.cbsnews.com/stories/2008/06/05/health/
Cumulative Number of Confirmed Human Cases of Avian Influenza A(H5N1) reported to WHO (updated 28th May 2008)
A(H5N1) avian influenza: timeline of major events (updated 2nd June 2008)
AVIAN INFLUENZA – ANIMAL HEALTH – UK
5th June 2008
Following the finding of a highly pathogenic strain of H7 avian influenza in a large poultry farm in Banbury, Oxfordshire in central UK, on 3rd June, the UK authorities have confirmed that the strain type of virus on the affected farm was H7N7. This information was reported to the OIE on 5th June.
All 25,000 birds on the affected premises have been culled as part of the infection containment measures, and a Temporary Control Zone with a 3km inner zone and a 10km outer zone have been established around the Infected Premises. No further cases associated with the outbreak have been reported
The UKs’ Health Protection Agency (HPA) has responsibility to manage the local public health response to the infection. The HPA has issued guidance to assist local units (1), and in this case includes contacting staff from the farm to verify health status and ensuring active health surveillance is undertaken. This guidance is somewhat less restrictive than would be followed for A(H5N1) viruses reflecting the somewhat lower risks to human health from A(H7) viruses and other non-H5 avian influenza viruses. Again to date there has been no reported human health event associated with this outbreak. However it’s important to remember that avian influenza A(H7N7) is the virus group that let to very large scale outbreaks in poultry in 2003. There were some humans infected at that time with very limited human to human transmission. Most of the infections were mild but there was one fatal infection, the only know fatality due to any avian influenza apart from A(H5N1).(2-4)
1) UK’s Health Protection Agency (HPA): Guidance for Health Protection Units on dealing with human health implications of avian influenza in poultry and wild birds. (http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1194947343802)
2) Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Koopmans M, Wilbrink B, Conyn M, Natrop G, van der Nat H, Vennema H, Meijer A, van Steenbergen J, Fouchier R, Osterhaus A, Bosman A.Lancet. 2004 Feb 21;363(9409):587-593
3) Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Kuiken T, Rimmelzwaan GF, Schutten M, Van Doornum GJ, Koch G, Bosman A, Koopmans M, Osterhaus AD. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome.Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1356-61. Epub 2004 Jan 26.
4) Bosman A ; Mulder YM ; Leeuw JRJ de Avian Flu Epidemic 2003: Public health consequences RIVM Report, Bilthoven, Netherlands 2004, http://www.rivm.nl/bibliotheek/rapporten/630940004.pdf
OIE official report, including location map (5th June 2008)
UK Defra news release: Avian Influenza outbreak in Oxfordshire: update (5th June) (http://www.defra.gov.uk/news/2008/080605c.htm).
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AVIAN INFLUENZA – ANIMAL HEALTH – HONG KONG S.A.R.
11th June 2008
ON 7th June, The Hong Kong authorities reported that environmental samples taken from cages in a poultry market have tested positive for A(H5N1). The Market was been declared an infected area and all the 2700 live chickens in the market were culled as a precaution, although no evidence of infection in the birds was found
Further investigation found positive samples in other markets in Hong Kong. Because more than one market were found to have samples tested positive of H5N1 avian influenza virus which may indicate that the virus might have the possibility of accumulating and spreading, the authorities have acted quickly to suspend all trading in live poultry, and has declared all poultry markets an infected premises. The HK Food and Environmental Hygiene Department is also culling and destroying all live poultry and poultry products in all market stalls.
In light of the findings, the Hong Kong Centre for health protection has activated a ‘serious response level’ threat to reflect the potentially increased risk to public health, and has also issued number of enhanced measures under the current Serious Response Level in public hospitals. This includes reminding all frontline hospital staff to stay vigilant for avian influenza, especially in patients who work in or have visited poultry markets and have close contact with poultry or wild bird. Increased general infection control provisions have also been implemented, such as reduced visiting hours in public hospitals, and requiring visitors and patients with respiratory symptoms to put on surgical masks in hospitals and clinics.
ECDC comment (12/6/08): It is important to highlight that to date, no bird has been found to be infected with A(H5N1) virus, although surveillance is ongoing and given the finding of the virus from environmental swabs, the positive identification of the virus in poultry should be expected. Hong Kong authorities have reacted very decisively and rapidly to contain potential infection in poultry, and to increase the threat level for public health; the measures are very precautionary given no positive finding in birds, but it should be recalled that Hong Kong is particularly sensitised to the public health risk from A(H5N1) following the first identification of virus in the region in 1997 and the 18 cases and 6 associated fatalities reported to be due to the virus at that time. The structure of live poultry trading in the region also means that it would be very difficult to eradicate the virus from poultry flocks if it became established, and the close contact between people and poultry would also present a significant risk to public health, even if the present virus remains poorly adapted to humans.
The high level of AI surveillance in Hong Kong is unprecedented, and this is what prompted the discovery of the virus and the subsequent precautionary reaction in this case. As explained, the precautionary response to A(H5N1) infection in Hong Kong is understandable, but it can give the impression that there is a dramatic increase in the overall public health risk from A(H5N1). So far, there is no evidence that this is the case.
See: Hong Kong SAR avian influenza website: (http://www.info.gov.hk/info/flu/eng/index.htm)
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AVIAN INFLUENZA – ANIMAL HEALTH – BANGLADESH
11th June 2008
The Bangladesh authorities reported to the OIE that A(H5N1) infection has identified in a further farm in Dhaka province. Over 4,600 birds have been either succumbed to infection or culled as part of the protection measures taken.
ECDC comment (12/6/08): This is an area that has seen many outbreaks of A(H5N1) in poultry in recent months, and the first human case from the country was confirmed on 28th May. It would appear that containment efforts are being made, although the fear persists that A(H5N1) infection will become established in the region.
See: OIE official report, including location map (11th June 2008)
SCIENTIFIC ADVANCES – AVIAN INFLUENZA- EPIDEMIOLOGY
Finding the real case-fatality rate of A(H5N1) avian influenza.
Li FCK, Choi BCK, Sly T, Pak AWP
J Epidemiol Community Health 2008; 62: 555-9.
The authors here are attempting to estimate the case-fatality rate of human H5N1 infections. They suggest three reasons that there may be an over-estimation of the CFR: 1. that mild and asymptomatic infections are missed; 2. that some countries are deliberately under-reporting mild cases; and 3. that should A(H5N1) become more transmissible its virulence and observed case fatality rate would decline. The paper then goes on to present evidence as to why all three reasons are unlikely to apply, for example noting that the limited amount of sero-epidemiology done around confirmed cases had failed to find mild or asymptomatic, that they did not consider countries were concealing mild cases and there was not prima facie scientific case to suggest that as transmissibility rises virulence must fall. They then decide that the best surveillance around cases were in Hong Kong in 1997 and Turkey in 2005/6 when the observed case fatality rates for confirmed cases were 14% and 33% respectively. They then simply state that this is in their view the real case fatality rate.
ECDC Comment (12/06/08): Occasionally a paper has such eye-catching in results that although the paper is not that substantial in itself ECDC has to feature and comment on the paper. Partially this is so that when the result is cited later a public domain critique exists.
The conclusion of this paper is unconventional. Having strongly argued against three reasons for thinking that case fatality rates would be an over-estimate the authors seem to lose confidence and seize on two outbreaks which give low case fatality rates without really saying why. Certainly surveillance in Hong Kong is good and especially good around ‘bird flu’. However the outbreak of A(H5N1) in 1997 was the first studied outbreak and of a virus that has evolved genetically since then.(1) It would seem odd to say that these first observations are more valid than later observations when the virus has moved on genetically. ECDC was involved in the outbreak in Turkey and knows just what difficult conditions were faced by the Turkish authorities. This was mostly an outbreak investigated without serology in the depths of the winter with extremely low temperatures in difficult operating conditions. Again it seems a strange outbreak to choose as the one that will have more valid results. The current observed CFR is high; around 67% and 75% for 2007 and 2008 WHO-confirmed cases respectively.(2) These rates probably can come down with early good treatment. At the 2007 WHO global consultation on A(H5N1) physicians from Egypt presented data with lower observed case fatality rates which followed from early treatment especially of children brought forward by their parents. The WHO data indicates a fatality rate of 44% (2,3) Certainly the CFR of human avian influenza A(H5N1) infections are high. From a human point of view avian influenza A(H5N1) remains a very nasty virus when it does infect, but that is not totally unexpected given that it is behaving like other severe zoonoses. The ECDC risk assessment still applies namely H5N1 viruses in humans currently remain “a group of influenza viruses of birds, poorly adapted to humans whom they find hard to infect except at high doses. They are dangerous as they are highly pathogenic in those few humans that do become infected, but then they generally do not transmit on to other humans.”. (4)
1) Webster RG, Govorka EA. H5N1 Influenza: Continuing evolution and spread. NEJM 2006; 355: 2174-77
2) WHO H5N1 cases WHO website http://www.who.int/csr/disease/avian_influenza/country/en/ (cited for May 28th)
3) Writing Committee of the second WHO consultation on clinical aspects of human infection with avian influenza A (H5N1) virus. NEJM 2008; 358: 261-73 http://content.nejm.org/cgi/reprint/358/3/261.pdf
4) ECDC Risk Assessment October 2005, Updated June 2006 http://www.ecdc.eu.int/Health_topics/Avian_Influenza/pdf/060601_public_health_risk_HPAI.pdf
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Public health developments
P.H. DEVELOPMENTS- PANDEMIC INFLUENZA- ANTIVIRALS
A Member State Independent Expert Committee (UK – Scientific Pandemic Influenza) publish an expert opinion on the content and deployment of an extended antiviral stockpile.
Following the announcement by the UK to increase the national antiviral stockpile to cover treatment for 50% of the UK population, the UK’s Scientific Pandemic Influenza Advisory Committee was asked by the UK Department of Health to build on earlier advice on antiviral stockpiling by considering four additional questions related to the make-up and use of an extended stockpile. These were:
- Are there any subgroups of the population in which Zanamivir might be the preferred option, even before the development of resistance?
- Can oseltamivir still be used even if resistance develops in the population as a whole or in specific groups?
- Should resistance to oseltamivir develop, are there specific sub groups for whom Zanamivir should be stockpiled?
- Does the difficulty in using the Diskhaler preclude the use of Zanamivir in certain subgroups or those with certain symptoms of flu?
The Committee has published their opinion on these questions. (1) Some of the main conclusions were that:
- Zanamivir would be a preferred treatment option in some specific groups where Oseltamivir has contra-indications and warnings associated with its use, including children under 18, and these with kidney dysfunction. Because of its limited systemic action, Zanamivir may also be more suitable for use in pregnant or lactating women, although it may be less effective than Oseltamivir if pandemic virus induced a wide systematic infection.
- If the virus had already developed resistant to an antiviral drug before being introduced into the UK, use of that drug would not be recommended.
- Stockpiling Zanamivir for use by health care workers would be important in order to ensure continuity of care even pandemic strains develop resistance to Oseltamivir.
- It would be justifiable to stockpile enough Zanamivir to protect other groups, including the traditional ‘at risk’ groups and children. However the viability of widespread use of Diskhalers would need to be investigated before this could be recommended.
- Diskhalers are difficult to use, and this prevents their use by several groups including those with cognitive impairment, motor impairment and young children.
ECDC Comment (12/06/08): Although the opinion is issued by UK experts, it has broad relevance to pandemic planning across the EU. The conclusions highlight both the scientific and practical limitations on the individual use of Zanamivir. The advice was requested to inform policy makers, and it remains unclear how this will be translated into UK pandemic planning; policy decisions around antiviral stockpiles are challenging and there are no easy answers. It seems sensible to at least consider the option of holding two types of antivirals in a stockpile. This in theory gives a broader base to offer protection and treatment against a pandemic strain, particularly if the strain develops resistance to one type of antiviral drug. This possibility always existed, but has been bought into focus following the recent finding of strains of H1N1 seasonal influenza that have developed resistance to oseltamivir and scientific developments of understanding the mechanisms underlying (2,3). However, there remain significant challenges in building a stockpile with two drugs types as it dramatically complicates how the drugs will be delivered and deployed. In its report on the status of pandemic preparedness in the EU the ECDC concluded that this in area that already needs further work in the Member States (4). Delivering two drug types, possibly in parallel, to different sub-populations in an emergency situation would need even more logistical planning.
1) UK Scientific Pandemic Influenza Advisory Committee (SPI): Statement providing scientific advice on stockpiling neuraminidase inhibitors (http://www.advisorybodies.doh.gov.uk/spi/spi2008-01neuraminidasestockpiling.pdf)
2) Lackenby A, Hungnes O, Dudman SG, Meijer A, Paget WJ, Hay A, Zambon MC Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe. Eurosurveillance 2008; 13 (5) Jan 31st 2008 http://www.eurosurveillance.org/edition/v13n05/080131_2.asp
3) Collins PJ, Haire LF, Lin YP, et al Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants. Nature (2008) May 14. [Epub ahead of print]
4) ECDC Technical report: Pandemic Influenza Preparedness in the EU/EEA
Status report as of Autumn 2007, Stockholm, December 2007
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Meetings and workshops
Birdflu2008: Avian Influenza and Human Health, Oxford, UK. 10-11 September 2008
The first annual Oxford avian influenza conference, BirdFlu2008, will address most aspects of basic and applied research on avian influenza viruses and their potential health and socio-economic impact on humans.
Conference information can be found at: http://www.libpubmedia.co.uk/Conferences/BirdFlu2008/Home.htm
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3rd ESWI European Influenza Conference, Vilamoura, Portugal. 14-17 September 2008.
The European Scientific Working group on Influenza (EWSI) - an independent group of European scientists promoting the study of influenza – will hold its third European Influenza Conference in the autumn of 2008.
Conference information can be found at: http://www.eswiconference.org/
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International symposium on viral respiratory disease surveillance. Seville, Spain 25-27th March 2009. International Society for Influenza and other Respiratory Virus Disease (ISIRV)
Conference information can be found at http://www.isirv.org/
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The ECDC influenza project team very much welcomes potential contributions to these web updates from EU/EEA member states particularly concerning public health developments and scientific published papers. This includes publications in non-English languages. These should be sent, preferably with a web-link, to Influenza@ecdc.europa.eu. If drawing to our attention a non-English language article for development, a short summary in English is appreciated. However, this is not essential because of its multi-national staff, ECDC can cope with most languages from within the EU.