PERSPECTIVE Birds and Influenza H5N1 Virus Movement to and within North America John H. Rappole* and Zdenek Hub?lekf Highly pathogenic avian influenza (HPAI) H5N1 expanded considerably during 2005 and early 2006 in both avian host species and geographic distribution. Domestic waterfowl and migratory birds are reservoirs, but lethality of this subtype appeared to initially limit migrant effectiveness as introductory hosts. This situation may have changed, as HPAI H5N1 has recently expanded across Eurasia and into Europe and Africa. Birds could introduce HPAI H5N1 to the Western Hemisphere through migration, vagrancy, and importation by people. Vagrants and migratory birds are not likely interhemispheric introductory hosts; import of infected domestic or pet birds is more probable. If reassort- ment or mutation were to produce a virus adapted for rapid transmission among humans, birds would be unlikely intro- ductory hosts because of differences in viral transmission mechanisms among major host groups (i.e., gastrointesti- nal for birds, respiratory for humans). Another possible result of reassortment would be a less lethal form of avian influenza, more readily spread by birds. Avian influenza virus A refers collectively to a group of viruses within the family Orthomyxoviridae that has a worldwide distribution and causes a variety of diseases in birds. Classification of influenza viruses is based on 2 gly- coproteins (antigens) characteristic of the group members: hemagglutinin, of which 16 forms are known; and neu- raminidase, of which 9 forms have been described. In 1997, a virulent, highly pathogenic avian influenza (HPAI) A virus, identified as the H5N1 subtype, was identified in samples taken in Hong Kong (7,2). This virus has spread to several localities in Asia and, since late 2005, Europe (5) and Afi-ica {4) (Table 1). HPAI H5N1 virus is found most commonly in domestic fowl, although as of late 2005, it 'Smithsonian Institution, Washington, DC, USA; and fAcademy of Sciences, Valtice, Czech Republic has been found in migratory and resident birds of several orders (mainly Anseriformes) and in pigs, civets, house cats, tigers, leopards, and humans (5). This virus poses a potential danger to human populations; 224 human cases of H5N1 avian influenza have been reported as of May 29, 2006; 127 of these cases were fatal (77). Its discovery in migratory birds is especially troubling because of the potential for rapid dispersal of the virus across continents and hemispheres. We review facts concerning outbreaks of H5N1; the species of birds, especially migrants, known to have been infected by this subtype; and available information on the ability of migrants to serve as reservoir or introductory hosts that move the virus from outbreak areas to new local- ities. On the basis of this information, we consider the avian pathways by which HPAI H5N1 might enter the Western Hemisphere and, once present, the likelihood that it will be able to disperse to new regions. We define migra- tory or migrant birds as those species that move annually between geographically separate breeding and wintering quarters. Migrating birds are those actually in the process of moving from 1 locality to another. Ecology of Influenza A Viruses Avian influenza A viruses are common and widespread in birds. Most viruses in this family attack the intestinal tract of the host preferentially and are spread mainly by shedding in host feces {18,19). Waterfowl, e.g., ducks, geese, and swans (Anseriformes), and shorebirds (Charadriiformes) are particularly susceptible because they are exposed to water that may be contaminated with infected fecal matter, especially at specific sites and sea- sons, when these birds congregate densely at relatively confined and shallow water bodies (Figure 1). A secondary mode of viral spread is consumption of infected avian host 1486 Emerging Infectious Diseases ? www.cdc.gov/eid ? Vol. 12, No. 10, October 2006 Birds and Influenza H5N1 Virus, North America Table 1. Geographic spread of highly pathogenic avian influenza H5N1 subtype since 1996 Date Event 1996 1st isolation; domestic geese, southern China (5) 1997-1998 Chickens, Hong Kong; 18 humans (6 deaths) (6) 1999 Geese, Hong Kong (7) 2001 Geese from China in Vietnam (8) Nov 2002 Hong Kong poultry, other bird species in or near zoologie parks (7) Feb 2003 Human travelers from Fujian Province (China) (9) Dec 2003-Nov 2005 Poultry (mainly chickens) and humans: South Korea, Vietnam, Thailand, Hong Kong, Cambodia, Laos, Indonesia, China, and Malaysia (6) Jan 2004 Wild birds: Hong Kong {10) Feb 2004 Birds in a zoo collection: Cambodia {10) Mar 2004 Wild bird: South Korea {10) Oct 2004 Bird smuggled from Thailand into Belgium {11) Apr-Jun 2005 Migratory birds: Qinghai Lake and Xinjiang Province, China {12) Jul-Oct 2005 Poultry and wild waterfowl: Novosibirsk, Altai, Kurgansk, Omsk, and Tyumen regions, Asian Russia {13,14) Aug 2005 Geese and other poultry: northern Kazakhstan, Tibet {13) Aug 2005 Migratory waterfowl: northern Mongolia {15) Aug-Oct 2005 Poultry and pigeons: Ural Territory, Russia {13) Aug 2005 Wild waterfowl: Kalmykia, European Russia {13) Oct 2005 Domestic turkeys: Western Asian turkey {13) Oct-Nov 2005 Poultry and wild migratory birds: Romania, Ukraine {13) Oct 2005 Wild birds: Thailand {15) Oct-Nov 2005 Poultry, wild birds, some humans: 7 Chinese provinces {15) Oct 2005 Migratory waterfowl: Croatia {13) Oct 2005 Poultry: Tula and Tambov regions, European Russia {14) Oct 2005 Quarantined birds from Taiwan in United Kingdom {16) Jan 2006 Humans: Iraq {15) Jan 2006 Poultry: Nigeria, India (Maharashtra) {15) Feb 2006 Migratory waterfowl: Bulgaria, Greece, Italy, Slovenia, Bosnia, Azerbaijan, Iran, Georgia, Germany, Switzerland, Austria, Hungary, France, Croatia, Slovakia, Bosnia {15) Feb 2006 Poultry: Egypt, Cameroon, Niger, Ethiopia {15) Mar 2006 Migratory birds: Sweden, Denmark, Serbia, Poland, Czech Republic {15) Mar 2006 Poultry: Afghanistan, Pakistan, Albania, Israel, Jordan, Lebanon {15) Apr 2006 Poultry: Burkina Faso, C?te d'Ivoire, Myanmar, Nigeria, Palestinian Autonomous Territories {15) May 2006 Poultry: Sudan; migratory birds: United Kingdom {15) parts by predators, including captive carnivores, avian rap- summer, where large concentrations gather for weeks to tors, and carrion-feeding vertebrates. Infection by most undergo the postbreeding, premigratory molt {J8). For avian influenza A strains appears to be asymptomatic for charadriiformes, the greatest viral transmission opportuni- the host {J8). Proportions of birds shedding active virus ties would likely be at stopover sites during fall migration, can be high (e.g., >30% in some Canadian duck popula- where tens of thousands of individual birds congregate to tions) among juvenile waterfowl gathered in large flocks feed and roost (20). on lakes and ponds during the summer postbreeding molt- ing period but decrease rapidly during southward migra- Avian Influenza in Humans tion, falling to 1% to 2% during winter {J8). Nevertheless, Humans and other mammals normally are not suscepti- shedding of active virus can remain as high as 0.25% by ble to infection by avian influenza A viruses. Nevertheless, individual birds among northbound spring migrants, suffi- several subtypes of avian influenza or bird-origin influen- cient to reinfect northern breeding populations {J8). za viruses have infected humans; 3 of these subtypes have Most birds appear to be more or less susceptible to >1 caused pandemics within the past century. At present, strain of avian influenza A, but rates of infection and lev- HPAI H5N1 is entirely an avian influenza subtype, els of susceptibility to the different viral subtypes vary Humans can become infected, but so far as is known, they among taxa. For instance, H3 and H6 subtypes are com- must inhale or ingest massive viral doses from excreta or mon in ducks, geese, and swans (Anseriformes), while H4, tissues of infected birds to do so. Although clinically ill H9, Hll, and HI3 subtypes are more prevalent in sand- humans have high death rates, =50%, passage of H5N1 pipers, terns, and gulls (Charadriiformes) (20). The best virus from human to human is rare (5). opportunities for viral transmission among large numbers The more humans infected with HPAI H5N1, the of anseriform hosts would likely be on lakes and ponds in greater the probability that reassortment with a human Emerging Infectious Diseases ? www.cdc.gov/eid ? Vol. 12, No. 10, October 2006 1487 PERSPECTIVE Figure 1. Saurus cranes {Grus antigone) over Naung Mung, Myanmar, in March 2006. influenza virus strain will occur and produce a lethal form that is spread readily between humans {18,19). However, viral interhost transmission strategies differ fundamentally for those viruses that primarily infect humans versus those that infect birds. Bird viruses have an affinity for the host's intestinal tract, and interhost transmission occurs mainly by fecal contamination of shared water bodies. Human viruses more often attack the respiratory system and depend on shedding in respiratory effluvia for interhost transfer. If, or when, a reassortment or mutation of HPAI H5N1 produces a virus capable of efficient horizontal transfer among humans, the new virus would likely not be particularly effective in transfer among birds; migrants likely would play little role in spread of such a virus. Vaccines produced to prevent human infection by H5N1 might not be effective against a new virus produced by reassortment. Birds as HPAI H5N1 Reservoirs and Introductory Hosts in the Old World The main reservoirs and introductory hosts for avian influenza A viruses in general are migratory waterfowl and domestic fowl {18,19). HPAI H5N1, however, causes high rates of disabling illness and death in most avian species (21). High rates of illness would prevent migrants from being introductory hosts, since sick wild birds normally cannot move far and do not survive long. Thus, perhaps not surprisingly, no evidence exists that migrants were intro- ductory hosts for H5N1 for several years after its initial appearance in Guangdong Province, People's Republic of China, in 1996. In fact, no deaths or even infections of migrants were reported until December 2002, when sever- al migrants and exotic birds were found dead at a Hong Kong park and zoologie garden (70). Of 3,095 outbreaks of HPAI H5N1 reported from December 2003 through February 2005, all involved captive birds or domestic fowl (6). Until early August 2005, only 2 outbreaks of HPAI H5N1 had been confirmed in migratory birds presumed to be completely separate from domestic fowl: Qinghai Lake and Xinjiang Province, China, (April, May 2005) {12) and Lakes Erhel and Khunt in northern Mongolia (August 2005) (75). However, that situation has changed, and sever- al new outbreaks have been recorded in migrants that were presumably separate from domestic fowl within the last few months (online Appendix; available from http://www.cdc. gov/ncidod/EID/voll2no 10/05-1577_app.htm), perhaps signaling genetic modification of the virus {19). Data based on observations of dead wild birds at sites where infections have broken out and negative results from subsequent extensive screening for seropositive or infected migrants around outbreak sites have indicated that HPAI H5N1 was lethal for most wild birds, at least until recently. Nevertheless, some studies have demonstrated that chick- ens, domestic ducks, and geese infected under laboratory conditions, as well as some wild birds exposed under qua- silaboratory conditions (e.g., birds fed, watered, and pro- tected at zoologie parks or gardens), survive infection and shed the virus in active form {10,22,23). The work by Komar et al. {24) on wild birds exposed to West Nile virus (WNV) under laboratory conditions may be instructive in this regard. These researchers found that in species like the fish crow {Corvus ossifragus), in which individual birds were known to have high death rates on exposure to the New York 99 subtype of WNV in the wild (on the basis of large numbers of birds found dead and failure to find free- flying birds captured that were seropositive), survival rates from exposure in the laboratory were 45%. When one con- siders that birds kept in a laboratory have ready access to food and water during their illness, as well as protection from inclement weather and predators, this finding perhaps is not surprising. However, wild birds associating with free- ranging domestic fowl at farm ponds, or captive exotic birds at city parks or zoological gardens, may receive some of the same benefits as laboratory birds, experiencing con- ditions conducive to survival of infection by HPAI H5N1. Recent detections of HPAI H5N1 in free-ranging migrants may be a result of heightened awareness and thus the virus could have been circulating in migrants, although undetected. This explanation is unlikely considering the extensive screening of blood and feces of migrants in the past several years in Europe, parts of Asia, and North America. These screenings have searched for birds seropositive for H5N1 and other avian influenza type A viruses. These searches have involved sampling thousands of birds of hundreds of species (25,26). The virus may also have changed to some degree (2,19), allowing higher sur- vival rates among some species of migrants. Both explana- 1488 Emerging infectious Diseases ? www.cdc.gov/eid ? Voi. 12, No. 10, October 2006 Birds and Influenza H5N1 Virus, North America tions may have some relevance to the current situation. In any event, some migratory birds may now be able to move HPAI H5N1 in active form over considerable distances (online Appendix). Increasing numbers of recent reports document apparent movement of the virus, whereas before April 2005, no evidence existed of HPAI H5N1 in free- ranging migratory birds distant from domestic fowl, despite years of sampling of tens of thousands of migrato- ry waterfowl of several species from wetland sites across the European continent (25). Possible Role of Birds in Arrival of HPAI H5N1 Avian Influenza in New World To date, HPAI H5N1 has not been recorded in the New World, although outbreaks of related avian influenza virus- es lethal to domestic fowl have occurred in Ontario, Canada, in 1966 (H5N9); Pennsylvania, United States in 1983 (H5N2); Puebla, Mexico, in 1994 (H5N2); Chile in 2002 (H7N3); Canada in 2004 (H7N3); and Texas, United States, in 2004 (H5N2) (27). All of these outbreaks occurred in domestic poultry and were controlled without further diffusion. We see 3 possible modes by which HPAI H5N1 might gain entry to the New World if birds were the introductory host: 1) normal interhemispheric migration, 2) vagrancy, and 3) legal and illegal importation of birds as explained in the following section. Normal Interhemispheric Migration Few individual birds within few species undertake reg- ular, interhemispheric migration. However, some do, and the waterfowl (Anseriformes, Charadriiformes, Ciconii- formes) could be introductory hosts for HPAI H5N1 to the New World (Table 2). Three pathways are used annually by a small number of waterfowl species to travel between the hemispheres: 1) Alaska-East Asia, in which birds that breed in Alaska winter in East Asia; 2) East Asia-Paciflc North America, in which birds that breed in northeast Asia winter along the Pacific Coast of North America; and 3) Europe-Atlantic North America, in which birds that breed in Iceland or northwestern Europe winter along the Atlantic Coast of North America (Figure 2, Table 2). Two lines of evidence argue against normal, interhemi- spheric migration as a likely mode of entry for HPAI H5N1 into the Western Hemisphere. First, as discussed previous- ly, data indicate that most infected individual birds of most species of migrants become extremely ill and either cannot migrate far in their weakened state or die at the place of infection. Second, investigation of the genetics of avian influenza viruses has shown that little natural interchange occurs between the Eastern and Western Hemispheres: each hemisphere appears to have an avian influenza virus community that is largely distinct (18). This fact is partic- ularly noteworthy when one considers that most avian influenza A viruses appear to be asymptomatic, and migrants readily transport them in infectious form, in stark contrast to the situation for HPAI H5N1. Presumably, the distinct nature of the avian influenza A community in each hemisphere results from the fact that the main reservoir for these viruses is migrants, and few migrants move regular- ly between the hemispheres (32). Vagrancy Perhaps a third or more of Eurasian waterfowl species have traveled into the Western Hemisphere as vagrants; some occur more regularly than others, including those list- ed in Table 2. However, all Eurasian vagrants are, by defi- nition, extremely rare in the New World (a few birds per decade). One mode of interhemispheric vagrancy is tropical storm systems that originate off the West African coast dur- ing the Atlantic hurricane season, which lasts from June to November each year. These systems can, and occasionally do, sweep up and transport Old World birds, especially waterfowl, across the Atlantic to the New World (route 4, Figure 2). Vagrancy is much rarer (by several orders of magnitude) than normal interhemispheric migration and seems an even less likely mode of entry for HPAI H5N1. Legal and Illegal Importations Human traffic in birds and bird products is the sole doc- umented means of HPAI H5N1 movement between geo- graphically separate regions to date (79). While migratory birds have been suspected of involvement, particularly in cases in which no obvious human interchange of infected birds or products has occurred, these conclusions are inferred (19). Thus, if HPAI H5N1 is to be kept out of the Western Hemisphere, control of legal and illegal imports should be the primary focus of prevention efforts. The legal importation of exotic birds has declined dra- matically in the United States since enactment of the 1992 Wild Bird Conservation Act. Nevertheless, 2,770 birds entered the country through the New York port of entry in 1999, including 323 pet birds and 2,447 commercial birds. In addition, 12,931 birds passed through in transit (S. Kaman, US Department of Agriculture [USDA], pers. comm.) Legal importations are controlled by USDA Animal and Plant Health Inspection Service and the US Fish and Wildlife Service. Most imported birds undergo a 30-day quarantine at USDA facilities located near each of the 3 allowed ports of entry: New York, Miami, and Los Angeles. Quarantine procedures include isolation in indoor, air-filtered cages and standard testing for common poultry diseases, including avian influenza. The number of illegally imported birds is not known. These birds are not subject to quarantine and testing and could be a mode of entry for HPAI H5N1. Hawk eagles from Thailand infected with the virus were recently detected while being Emerging Infectious Diseases ? www.cdc.gov/eid ? Voi. 12, No. 10, October 2006 1489 PERSPECTIVE smuggled into Belgium (77). Although these birds were detected and quarantined, they serve as an example of how such imports could spread the virus. Species com- monly associated with the transhemispheric bird trade are listed in Table 2. If birds turn out to be responsible for entry of HPAI H5N1 into the Western Hemisphere, illegal import of an infected bird or bird product seems the most likely mode of entry. We base this conclusion on the fact that illegally imported birds, unlike infected, free-flying migrants, are provided food and water ad libitum and protected from predators, greatly increasing their chances of survival in an infectious state. Furthermore, these birds often end up in close association with other, similarly protected birds, Table 2. Known interhemispheric movement by migratory or vagrant waterfowl (Ciconiiformes, Anseriformes, Charadriiformes), domestic bird trade (Galliformes), or exotic bird trade (Galliformes, Psittaciformes) from Eurasia to North America* Species Likely mode of entry Bean goose {Anser fabalis) Greylag goose {A. anser) (domestic) Whooper swan {Cygnus cygnus) Falcated duck {Anas falcate) Eurasian wigeon {A. penelope) Mallard {A. platyrhynchos) (domestic and wild) Garganey {A. querquedula) Green-winged teal {A. crecca) Common pochard {Aythya ferina) Tufted duck {Aythya fuligula) Smew {Mergellus albellus) Jungle fowl {Gallus gallus) (domestic) Pfieasants (Phasianidae) Quail {Coturnix coturnix) Wild turkey {Meleagris gallopavo) (domestic) Red-faced cormorant {Phalacrocorax urile) Gray fieron {Ardea cin?rea) Little egret {Egretta garzetta) Cattle egret {Bubulcus ibis) Eurasian kestrel {Falco tinnunculus) Northern lapwing {Vanellus vanellus) Mongolian plover {Cliaradrius mongolus) Common ringed plover (C. Iiiaticula) Eurasian dotterel (C. morinellus) Spotted redshank {Tringa erythropus) Wood sandpiper {T. glareola) Gray-tailed tattler {l-leteroscelus brevipes) Bar-tailed godwit {Limosa lapponica) Red-necked stint {Calidris ruficollis) Little stint (C. minuta) Sharp-tailed sandpiper (C. acuminate) Ruff {Phiiomachus pugnax) Little gull {Larus minutus) Black-fieaded gull (L. ridibundus) Black-tailed gull (L. crassirostris) Yellow-legged gull (L. cachinnans) Slaty-backed gull (L. schistisagus) Common tern {Sterna liirundo) Rock pigeon {Columba livia) (domestic) Oriental turtle-dove {Streptopelia orientalis) European turtle-dove (S. turtur) Eurasian collared-dove (S. decaocto) Parrots {Psittacidae) Migration! Exotic and domestic bird trade Migration! Migration,! exotic bird trade, zoos, vagrant Migration,tt exotic bird trade, zoos Exotic and domestic bird trade Migration,tt exotic bird trade, zoos Migrationtt Migrationt Migrationtt Migrationt Domestic bird trade Exotic bird trade, zoos Domestic bird trade Domestic bird trade Migration? Vagrant Vagrant Vagrant Vagrant Vagrant Migrationt Migration? Migration? Migrationt Migrationt Migrationt Migration? Migration? Vagrant Migrationt? Migrationtt Migrationt Migrationtt Vagrant Vagrant Migrationt Vagrant Exotic bird trade Exotic bird trade Exotic bird trade Exotic bird trade Exotic bird trade ?Species shown in bold are known to have been infected with highly pathogenic avian influenza H5N1. Sources for information on migrant or vagrant status are Kessel and Gibson (28), Palmer (29), and the American Ornithologists' Union {30). Nomenclature follows the American Ornithologists Union checklist {30) to the degree possible. Supplementary source: Rasmussen and Anderton (31). tRoute 2. See Figure 2. JRoute 3. See Figure 2. ?Route 1. See Figure 2. 1490 Emerging Infectious Diseases ? www.cdc.gov/eid ? Vol. 12, No. 10, October 2006 Birds and Influenza H5N1 Virus, North America '?'-^^?>x sharing the same food or water, a situation that provides ample opportunity for viral transmission. Possible Role of Birds in Movement of HPAI H5N1 in Western Hemisphere Movement of HPAI H5N1 by sale of infected domestic fowl or poultry products in the United States and Canada is unlikely, given existing regulations. Thus, a major mode of HPAI spread available in much of Eurasia would be ruled out. Also, most domestic fowl are kept separate from wild migratory waterfowl in both countries, which would rule out a second major mode of introduction and cross- infection. Mixing of wild migratory birds with captive, exotic birds is relatively common, however, at North American zoos. Birds in such exhibits should be screened regularly for H5N1 or whatever HPAI virus is in circula- tion during a given year. The HPAI H5N1 subtype of avian influenza A causes high mortality rates in most wild birds, at least in its pres- ent form. The situation is similar to that found for the form of WNV introduced into the Western Hemisphere in 1999 (24,32-34). Even under conditions in which food, water, and protection from predators are provided, death rates are high. These kinds of death rates could result if the current form of HPAI H5N1 were introduced into New World bird populations. In such a scenario, migrants might not be capable of moving the virus far from its point of introduc- tion, at least initially. Also, the die-offs occurring at the site of entry likely would be obvious to wildlife disease moni- tors, which would allow for rapid quarantine. However, if the H5N1 virus were introduced into the Western Hemisphere, migratory birds, particularly anseriforms (ducks, swans, geese), might serve as dispersal agents, especially if the virus were to change to a less lethal form through reassortment or mutation. A key difference between mosquitobome WNV and birdbome HPAI H5N1 is the virtual absence of effective reservoir hosts other than birds for the latter. WNV can be maintained without birds because infected mosquitoes can pass active virus to subsequent generations through verti- Figure 2. Map of known routes for nat- ural interhemispheric bird movement: route 1, migrants breeding in Alasita and wintering in East Asia; route 2, migrants breeding in East Asia and wintering along the Pacific Coast of North America; route 3, migrants breeding in Iceland or northwestern Europe and wintering along the Atlantic Coast of North America; route 4, vagrants from West Africa carried by tropical storm systems across the Atlantic to eastern North America. cal transmission (35). So far as is known, no alternative to birds exists as major reservoir hosts for HPAI H5N1. An additional consideration concerning the future of HPAI H5N1, should it gain wide circulation in migratory birds, is the possibility of infection of a bird already infect- ed with another form of avian influenza virus. Such infec- tion could result in reassortment and production of a new virus, possibly less lethal than HPAI H5N1 but more read- ily spread. Conclusions HPAI H5N1 spread rapidly across Eurasia during 2005 for reasons that are not entirely understood. Despite this rapid movement, effective introduction (i.e., under condi- tions allowing its spread) of the virus to the New World through migratory or vagrant birds seems unlikely. Few individual members of few waterfowl species migrate between hemispheres, and should a bird make the journey while shedding sufficient active virus to infect birds in the Western Hemisphere, newly infected birds would probably die before being able to transport the virus from the entry site. If spread of HPAI H5N1 to the New World occurs in its current form (e.g., through domestic or pet bird trade or smuggling), it should be readily detectable because of the large number of dead native birds likely to result. However, the virus is changing (19), and a modified H5N1 virus introduced into the Western Hemisphere could be moved more readily by migratory waterfowl. If this event were to occur, the virus should be amenable to control through isolation and quarantine. If viral reassortment or mutation occurs to produce a new virus that is readily transmissible to humans, the role of birds in general and migrants in particular may be moot because of the funda- mentally different methods of infection favored by viruses infecting humans and birds. Viruses infecting birds prefer- entially attack the intestinal tract and are shed with the feces; by contrast, human viruses mainly attack the respi- ratory tract and are shed with respiratory effluvia. If HPAI H5N1 were to gain wide circulation among migrants, it might infect a bird already infected with another form of Emerging Infectious Diseases ? www.cdc.gov/eid ? Vol. 12, No. 10, October 2006 1491 PERSPECTIVE avian influenza A and undergo r?assortaient to produce a low-pathogenic form that is more readily spread. Dr Rappole is a research scientist with the Smithsonian National Zoological Park's Conservation and Research Center. His principal research interests are migratory bird ecology and evolution, sub-Himalayan omithogeography, and avian conser- vation. Dr Hub?lek is a scientist at the Academy of Sciences of the Czech Republic. He is interested in the ecology of arthropod- borne human pathogenic viruses and bacteria. References 1. Li KS, Guan Y, Wang J, Smith G, Xu K, Duan L, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature. 2004;430:209-13. 2. Zhou NN, Shortridge K, Claas E, Krauss S, Webster R. Rapid evolu- tion of H5N1 influenza viruses in chickens in Hong Kong. J Virol. 1999;73:3366-74. 3. Fauci AS. Pandemic influenza threat and preparedness. Emerg Infect Dis. 2006;12:73-7. 4. Enserink M. H5N1 moves into Africa, European Union, deepening global crisis. Science. 2006;311:932. 5. Xu X, Subbarao K, Cox N, Guo Y. Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: simi- larity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Virology. 1999;261:15-9. 6. Morris R, Jackson R. Epidemiology of H5N1 avian influenza in Asia and implications for regional control. Rome: Food and Agricultural Organization of the United Nations; 2005. 7. Sims LD, Ellis T, Liu K, Dyrting K, Wong H, Peiris M, et al. Avian influenza in Hong Kong 1997-2002. Avian Dis. 2003;47:832-8. 8. Nguyen DC, Uyeki T, Jadhao S, Maines T, Shaw M, Matsuoka Y, et al. Isolation and characterization of avian influenza viruses, including highly pathogenic H5N1, from poultry in live bird markets in Hanoi, Vietnam, in 2001. J Virol. 2005;79:4201-12. 9. Ng EK, Cheng P, Ng A, Hoang T, Lim W. Influenza A H5N1 detec- tion. Emerg Infect Dis. 2005;11:1303-5. 10. Ellis TM, Bousfield R, Bisset L, Dyrting K, Luk G Tsim S, et al. Investigation of outbreaks of highly pathogenic H5N1 avian influen- za in waterfowl and wild birds in Hong Kong in late 2002. Avian Pathol. 2004;33:492-505. 11. Van Borm S, Thomas I, Hanquet G Lambrecht B, Boschmans M, DuPont G et al. Highly pathogenic H5N1 influenza virus in smug- gled Thai eagles, Belgium. Emerg Infect Dis. 2005;11:702-5. 12. Chen H, Smith G Zhang S, Qin K, Wang J, Li K, et al. H5N1 virus outbreak in migratory waterfowl. Nature. 2005;436:191-2. 13. World Health Organization. H5N1 avian influenza timeline: 23 Get 2005 [cited 2006 Get 23]. Available from http://www.who.int/entity/ csr/disease/avian_influenza/Timeline_28_ 1 Oa.pdf 14. Brown I, Gaidet N, Guberti V, Marangon S, Olsen B, editors. Mission to Russia to assess the avian influenza situation in wildlife and the national measures being taken to minimize the risk of international spread. Office International des Epizootics 2005 [cited 2005 Oct 23]. Available from http://www.oie.int/downld/Missions/2005/Report Russia2005Final2.pdf 15. Office International des Epizootics. Update on avian influenza in ani- mals (type H5) 24 May 2006 [cited 2006 May 24]. Available from http://www.oie.int/downld/AVIAN%20INFLUENZA/A_AI- Asia.htm 16. Department for Environment, Food, and Rural Affairs (DEFRA), United Kingdom. Epidemiology report on avian influenza in a quar- antine premises in Essex [cited 2006 May 29]. Available fiom http://www.defra.gov.uk/animalh/diseases/notifiable/disease/ai/pdf/ai -epidemrep 111105.pdf 17. World Health Organization (WHO). Cumulative number of con- firmed human cases of avian influenza A/ (H5N1) reported to WHO as of 29 May 2006 [article in French] [cited 2006 May 29]. Available from http://www.who.int/csr/disease/avian_influenza/country/cases table_2006_05_29/en/index.html 18. Webster RG, Bean W, Gorman O, Chambers T, Kawaoka Y Evolution and ecology of influenza A viruses. Microbiol Rev. 1992;56:152-79. 19. Webster RG, Peiris M, Chen H, Guan Y H5N1 outbreaks and enzoot- ic influenza. Emerg Infect Dis. 2006;12:3-8. 20. Kawaoka Y, Chambers T, Sladen W, Webster G Is the gene pool of influenza viruses in shorebirds and gulls different fiom that in wild ducks? Virology. 1988;163:247-50. 21. Perkins LE, Swayne D. Comparative susceptibility of selected avian and mammalian species to a Hong Kong-origin H5N1 high-patho- genicity avian influenza virus. Avian Dis. 2003;47:956-67. 22. Shortridge KF, Zhou N, Guan Y, Gao P, Ito T, Kawaoka Y, et al. Characterization of avian H5N1 influenza viruses fiom poultry in Hong Kong. Virology. 1998;252:331^2. 23. Hulse-Post DJ, Sturm-Ramirez K, Humberd J, Seiler P, Govorkova E, Krauss S, et al. Role of domestic ducks in the propagation and bio- logical evolution of highly pathogenic H5N1 influenza viruses in Asia. Proc Nati Acad Sei USA. 2005;102:10682-7. 24. KomarN, Langevin S, Hinten S, Nemeth E, Edwards D, Hettler B, et al. Experimental infection of North American birds with the New York 1999 strain of West Nile virus. Emerg Infect Dis. 2003;9:311-22. 25. Munster VJ, Wallensten A, Baas C, Rimmelzwann G, Sch?tten M, Olsen B, et al. Mallards and highly pathogenic avian influenza ances- tral virases, northern Europe. Emerg Infect Dis. 2005; 11:1545-51. 26. Spackman E, Stallknecht D, Siemens R, Winker K, Suarez D, Scott M, et al. Phylogenetic analyses of type A influenza genes in natural reservoir species in North America reveals genetic variation. Vims Res. 2005;114:89-100. 27. Werner 0. Klassische Gefluegelpest?eine Uebersicht. Berl Munch Tierarzfl Wochenschr. 2006;119:140-50. 28. Kessel B, Gibson D. Status and distoibution of Alaska birds. Studies in Avian Biology. 1978;1:1-100. 29. Palmer R. Handbook of North American birds. Vol 2. New Haven (CT):Yale University Press; 1976. 30. American Ornithologists' Union (AOU). The A.O.U. check-list of North American birds. 7th ed. Washington: American Ornithologists' Union; 1998. 31. Rasmussen P, Anderton J. Birds of South Asia: the Ripley guide. Barcelona: Lynx Ed.; 2005. 32. Rappole JH, Dertickson S, Hub?lek Z. Migratory birds and spread of West Nile viras in the Western Hemisphere. Emerg Infect Dis. 2000;6:319-28. 33. Bernard KA, Maffei J, Jones S, Kauffman E, Ebel G Dupuis A II, et al. West Nile viras infection in birds and mosquitoes, New York State, 2000. Emerg Infect Dis. 2001;7:679-85. 34. Brault AC, Langevin S, Bowen R, Panella N, Biggerstaff B, Miller B, et al. Differential viralence of West Nile strains for American crows. Emerg Infect Dis. 2004;10:2161-8. 35. Nasci RS, Savage HM, White DJ, Miller JR, Cropp BC, Godsey MS, et al. West Nile viras in overwintering Culex mosquitoes. New York City, 2000. Emerg Infect Dis. 2001;7:742-7. Address for correspondence: John H. Rappole, 1500 Remount Rd, Front Royal, VA 22630, USA; email: rappolej@si.edu 1492 Emerging Infectious Diseases ? www.cdc.gov/eid ? Vol. 12, No. 10, October 2006