Highly pathogenic avian influenza A/H5N1 in birds within the EU - Implications for Public Health

Since the later part of June 2007, three European Union (EU) Member States (Czech Republic, Germany, and France) have recorded cases of highly pathogenic avian influenza (HPAI) of the subtype A/H5N1 in bird populations.

On 21 June, authorities in the Czech Republic confirmed an outbreak of HPAI A/H5N1 in a domestic poultry flock in the Pardubicky region in the centre of the country [1]. A few days later a second infected flock, located 4km from the first, was identified through the enhanced surveillance of flocks in the area that was introduced after discovery of the first infected premise [2]. Subsequently, virus was isolated from a wild bird (swan) found dead on 28 June in the Jihomoravsky region in south of the country, near the border to Austria [3].

At almost the same time, on 26 and 28 June, German authorities reported that HPAI A/H5N1 had been identified in wild birds in two locations in Germany; six wild birds (five swans and one Canada goose) in Bavaria in southern Germany [4], and three wild swans in Saxony in eastern Germany [5].

On 5 July, France also confirmed the first occurrence this year of three wild swans infected with influenza A/H5N1. They were found in the Mosel region in the north-east of France [6].

Samples from the infected birds from all three countries were identified as part of the EU supported active surveillance programme for avian influenza in wild birds, which requires all EU Member States to test wild birds for avian influenza viruses in order to provide an early warning of the presence of the virus in the EU [7].

Virus strain analysis
Initial phylogenetic analysis of the virus subtype from the outbreaks, conducted by the EU’s Community Reference Laboratory for Avian influenza in the United Kingdom (UK) and the Friedrich-Loeffler Institut in Germany, suggests that the viruses recently identified in the Czech Republic and Germany are highly similar. However, they are of different origin from those identified during other EU poultry outbreaks earlier this year (UK and Hungary) and in 2006. Instead, the current virus is more closely related to a lineage originating from the Middle East (including Bangladesh, Pakistan and Azerbaijan) and Russia [8]. However, as for all H5N1 viruses to date, there has been no indication of a significant phylogenetic change which would alter the behaviour of the A/H5N1 virus in humans.

Control measures in animals
In accordance with EU animal health legislation prompt and vigorous animal disease control measures have been taken in both countries. Understandably, measures are more stringent for outbreaks in domestic poultry where the onus is to remove the source of infection, and to dampen down or stamp out the level of virus in the vicinity as quickly as possible so as to prevent spread. In this case legislation dictates a containment strategy involving culling all birds on the affected premises followed by cleaning and disinfection. In addition, two roughly concentric zones must be established around the affected farms: A 3km protection zone and a 10km surveillance zone, which constitute Area A (high risk), and a surrounding buffer zone called area B (lower risk) [9].

If A/H5N1 is discovered in wild birds, EU legislation allows a less stringent approach but still requires that a control area and a surrounding monitoring area are established around the infected birds. This can be adapted on a case by case basis following a risk assessment taking into account the local geographical, ecological and epidemiological circumstances. Measures are aimed at preventing the spread of avian influenza from wild birds to poultry or other captive birds and include strengthening of on-farm biosecurity and disease awareness, temporary banning of wild bird hunting and restrictions on the movement of poultry and poultry products [10].

Epidemiological investigations as to the possible source of the domestic poultry outbreaks in the Czech Republic are ongoing. No cases of influenza A/H5N1 have been recorded in wild birds in the vicinity of any of the domestic poultry cases in 2007 (the case of A/H5N1 reported in a wild bird in the Czech Republic was over 150km to the south of the infected farms). However, the fact that the outbreaks in domestic poultry coincided with the first reports of cases in wild birds in the EU in 2007 is probably more than a coincidence. It may indicate that the virus remains present intermittently in wild bird populations within some Member States. This also places domestic poultry flocks at risk. The high genetic similarity of the strain in wild and domestic birds in the current outbreaks is at least consistent with interaction between wild birds and domestic poultry [8].

General implications
The re-emergence of influenza A/H5N1 in EU bird populations is of concern, but not an unexpected development since A/H5N1 viruses are highly persistent across the world. In some countries (all outside Europe) the viruses are now endemic. However, in other areas like the European Member States, they are appearing intermittently through uncontrollable movements of wild birds and perhaps also illicit or poorly controlled poultry trading [11]. The fact that active surveillance has been underway throughout the EU since 2002, and was increased in 2006 and 2007, and the fact that the cases described were the first isolations of A/H5N1 in wild birds this year, suggest that infection is neither as widespread nor as intense as in the early spring of 2006. However, the cases in wild birds are a timely reminder to all Member States to continue veterinary surveillance activities in bird populations (wild and domestic). This provides an essential early warning of the presence of the virus. If it is found in birds, it is vital that containment measures are rapidly deployed to control infection to prevent the virus from becoming established in domestic poultry. This is important in order to preserve the health of animals, and also to minimise the risk of human exposure to the virus.

Public health implications
Wherever cases of avian influenza are suspected, close collaboration between public health specialists and veterinarians remains crucial. This is especially the case for A/H5N1 because, although the virus is predominantly an infection in animals, and to date it has proved very difficult to transmit from birds to man, it has a high case fatality rate in those humans that become infected 11]. The aim is to ensure that people that have close contact with infected birds are given appropriate levels of advice and support. Because the recent incident in the Czech Republic involved outbreaks in domestic poultry, with large numbers of potentially infected animals requiring culling to minimise the spread of infection, public health authorities have been actively involved in

The cases in Germany occurred in individual wild birds and hence the risk of potential human exposure was much lower than in cases involving infected domestic poultry. However, there has been a cluster of human cases associated with slaughtering and plucking of feathers from wild birds that were suspected to have been infected with A/H5N1 (swans in Azerbaijan). This indicates that there is potential human health risk from wild birds, although it is likely to be low, and very dependant on how birds are handled and the precautions taken (12). It is however important that general precautions messages are communicated to the population to avoid handling birds found dead, and, as demonstrated in Germany, that authorities engage with those individuals that may have handled infected wild birds to advise them of how to protect themselves, the need to monitor their health, and provide advice and reassurance as necessary, along with antiviral prophylaxis if considered necessary. The recent outbreak of low pathogenicity avian influenza A/H7N2 in the UK has shown how people with home and hobby flocks can easily be infected if they are unaware of the risk [14].

Since the autumn of 2005, ECDC has been producing technical guidelines for minimising the risk of humans acquiring avian influenza (specifically H5N1) from exposure to infected birds or animals. A portfolio of guidance documents and risk assessments on other public health aspects of A/H5N1 is available for public health authorities and the public (Table) [15]. These documents highlight the importance of removing the source of infection as quickly as possible, while also implementing risk-minimising public health measures. ECDC has also produced a more general risk assessment of the public health risk posed by highly pathogenic avian influenza viruses emerging in Europe, with specific reference to type A/H5N1 [12].

Pandemic Risk
The three pandemics of the 20th century all had their origins to varying extents in genetic material introduced from avian into human influenza viruses, with the virus that caused the 1918 Spanish Influenza being the one most closely related to an avian strain [16]. There is no prima facie reason why the genes in A/H5N1 should contribute to the next pandemic rather than other avian influenzas (H2, H7, H9, etc.) that are currently circulating. What makes scientists and public health officials more nervous about A/H5N1 is its unprecedented mortality rate in humans of over 60%. Unlike most other avian influenza viruses it is exceptionally persistent in birds and keeps coming into contact with humans in countries where it is endemic in domestic birds [11,12]. Therefore the EU is sensibly preparing for any influenza pandemic, while watching influenza A/H5 viruses in particular [17].

Conclusions
Influenza A/H5N1 viruses 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´ [11]. This, together with veterinary measures and application of public health guidelines, is probably the reason why to date influenza A/H5N1 infection in wild and domestic birds in Europe has not resulted in human infections. However, there is no room for complacency. Ongoing vigilance, control of infection in poultry, communication to those at risk, and prompt response (case finding and management) to human cases remain the cornerstones of protecting humans against A/H5N1 viruses.

References:
  1. OIE. Highly pathogenic avian influenza, Czech Republic (Pardubicky region 22 June). Available from: http://www.oie.int/wahid-prod/public.php?page=single_report&pop=1&reportid=5626 (accessed 4 July 2007).
  2. OIE. Highly pathogenic avian influenza, Czech Republic ( Pardubicky region 29June). Available from: http://www.oie.int/wahid-prod/public.php?page=single_report&pop=1&reportid=5650 (accessed 4 July 2007).
  3. OIE. Highly pathogenic avian influenza, Czech Republic (Jihomoravsky region 29 June). Available from: http://www.oie.int/wahid-prod/public.php?page=single_report&pop=1&reportid=5654 (accessed 4 July 2007).
  4. OIE. Highly pathogenic avian influenza, Germany (Bavaria 26 June). Available from: http://www.oie.int/wahid-prod/public.php?page=single_report&pop=1&reportid=5632
  5. OIE. Highly pathogenic avian influenza, Germany (Saxony 28 June). Available from: http://www.oie.int/wahid-prod/reports/en_fup_0000005646_20070628_144439.pdf
  6. Le site interministériel de préparation à un risque de pandémie grippale. Présence du virus H5N1 sur trois cygnes en Moselle. [In French]. 5 July 2007. Abailable from: http://www.grippeaviaire.gouv.fr/article.php3?id_article=434 (accessed 5 July).
  7. European Commission, DG Health and Consumer Protection. Wild bird surveillance in the EU: See Guidelines for AI surveillance in wild birds and poultry. Available from: http://ec.europa.eu/food/animal/diseases/controlmeasures/avian/eu_resp_surveillance_en.htm
  8. Starick E, T Harder T, Beer M,Mettenleiter T, Brown I, Banks J. ProMed Avian Influenza (118): Czech-German Virus Sequence. Available from: http://www.promedmail.org/pls/promed/f?p=2400:1001:17333712346019691154::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,38169
  9. Council Directive 2005/94/EC of 20 December 2005 on Community measures for the control of avian influenza and repealing Directive 92/40/EEC. Available from: http://eur-lex.europa.eu/LexUriServ/site/en/oj/2006/l_010/l_01020060114en00160065.pdf
  10. Commission Decision 2006/563/EC of 11 August 2006 concerning certain protection measures in relation to highly pathogenic avian influenza of subtype A/H5N1 in wild birds in the Community and repealing Decision 2006/115/EC. Available from: http://eur-lex.europa.eu/LexUriServ/site/en/oj/2006/l_222/l_22220060815en00110019.pdf
  11. Food and Agriculture Organization of the United Nations. Background on Avian Influenza. Available from: http://www.fao.org/avianflu/en/background.html
  12. ECDC technical report: The Public Health Risk from Highly Pathogenic Avian Influenza Viruses Emerging in Europe with Specific Reference to type A/H5N1 Version June 1st 2006. Available from: http://ecdc.europa.eu/Health_topics/Avian_Influenza/pdf/060601_public_health_risk_HPAI.pdf
  13. WHO Human avian influenza in Azerbaijan, February–March 2006 Weekly Epidemiological Record 2006 81: 183-188. Available from: http://www.who.int/wer/2006/wer8118/en/index.html
  14. Editorial team Avian influenza A/(H7N2) outbreak in the United Kingdom http://www.eurosurveillance.org/ew/2007/070531.asp#2
  15. ECDC technical report: Avian influenza Portfolio - Collected risk assessments, technical guidance to public health authorities and advice to the general public, Stockholm, June 2006. Available from: http://www.ecdc.europa.eu/documents/pdf/up/ECDC_TR_Avian%20Flu%20Portfolio.pdf. See also: http://ecdc.europa.eu/Health_topics/Avian_Influenza/Guidance.html
  16. Taubenberger JK, Morens DM. 1918 influenza: the mother of all pandemics. Emerg Infect Dis. 2006 Jan;12(1):15-22. Available from: http://www.cdc.gov/ncidod/EID/vol12no01/05-0979.htm
  17. Influenza team (ECDC). Pandemic preparedness in the European Union – multi-sectoral planning needed. Euro Surveill 2007;12(2):E070222.1. Available from: http://www.eurosurveillance.org/ew/2007/070222.asp#1