The Avian Influenza 

H5N1 Threat

A highly pathogenic strain of avian 

influenza called H5N1 has caused 

mortality in over 40 species of wild 

birds including herons, storks and 

falcons in Asia. Millions of domestic 

poultry have either died or been culled 

in Asia because of outbreaks of highly 

pathogenic avian influenza (HPAI). 

Concern about wild birds infected 

with H5N1 increased when migratory 

waterfowl, including bar-headed geese, 

brown-headed gulls and great blackheaded gulls, began dying at Qinghai 

Lake Nature Reserve in western China 

and were discovered in May 2005. 

Over 6,000 birds have died so far. 

Studies showed that these birds were 

infected with HPAI H5N1 and that the 

Qinghai H5N1 strain appears to be a 

new recombinant virus, combining 

genetic material from at least two other 

HPAI H5N1 strains. It is unknown 

whether waterfowl and shorebird 

species infected with the current strains 

of H5N1 will become reservoirs and 

whether they will become carriers of the 

virus during migration. 

Typically, wild birds, such as migratory 

waterfowl, rarely show signs of the 

disease. However, some strains, such 

as H5N1, can cause serious illness and 

mortality in commercial poultry flocks. 

Not only is this strain of avian influenza 

in Asia highly pathogenic to domestic 

poultry, it can directly infect people and is 

capable of causing mortality in wild birds. 

There is growing concern that H5N1 may 

evolve into a strain that could spread over 

a larger geographical area by infecting 

migratory waterfowl and/or transmit 

efficiently from human to human, leading 

to a global pandemic.

Influenza can be divided into three groups 

(Types A, B, and C). Type A virus causes 

infection in birds (referred to as avian 

influenza or “bird flu”), humans, and some 

mammals, such as pigs; Type B is found 

exclusively in people; and Type C occurs 

in humans and pigs. Two proteins on the 

surface of Type A, hemagluttinin (HA) 

and neuraminidase (NA), are essential 

for infectivity. Protective immunity is 

developed when antibody is developed 

against these proteins, which are the 

basis of influenza vaccines. There 

are 16 different types of HA and 9 

different types of NA known. Human 

infections have been caused mainly by 

influenza viruses containing the H1, 

H2 and H3, and N1 and N2 proteins. In 

2004–2005, H1N1 and H3N2 were the 

main influenza A strains circulating in 

humans. 

Wild birds, especially shorebirds and 

waterfowl, are the natural reservoir 

of influenza A viruses. The birds and 

the virus have become well-adapted to 

each other over time; infection does 

not usually cause overt disease in wild 

birds. Unlike in humans, where only a 

limited variety of influenza subtypes 

are present, viruses of all HA and NA 

subtypes are found in aquatic birds. 

The viruses replicate mainly in the 

intestinal tract of aquatic birds and are 

transmitted in the feces. Thus, unlike 

human-to-human transmission, which 

is mainly via aerosol, transmission in 

aquatic birds is by the fecal-oral route. 

Avian influenza strains from wild birds 

usually cause mild, inapparent disease 

in domestic poultry and are designated 

low path avian influenza viruses 

(LPAI). Commercial poultry farms raise 

thousands of birds in close proximity, 

which allows avian influenza viruses to 

replicate efficiently. As the influenza 

viruses change during replications in 

Humans

Humans

Domestic

Fowl

Shorebirds

Mammals

Wa (primarily swine) terfowl

H5N1 H5N1

Natural

Reservoir

Figure 1. Possible transmission pathways for avian influenza. 

U.S. Department of the Interior

U.S. Geological Survey

August 2005

FS 2005–3146 Printed on recycled paper

Current facts and future concerns about Highly 

Pathogenic Avian Influenza H5N1.

Bar-headed goose. Many bar-headed geese died in 

an H5N1 outbreak in Qinghai Lake Nature Reserve 

in China.

 Wildlife Information Network
the domestic poultry, highly pathogenic 

avian influenza (HPAI) strains can arise, 

resulting in severe disease and high 

mortality. 

The genetic material of the influenza 

A virus is constantly changing and 

small-scale mutations (genetic drift) 

in the HA and NA proteins that alter 

antibody recognition lead to viruses 

that can evade the immune response. 

Although slightly different, viruses 

with such genetic drifts may still belong 

to the same subtype. For example, 

these two subtypes, A/chicken/

Shantou/423/2003 (H5N1) and A/barheaded goose/Qinghai/5/2005 (H5N1) 

are still considered H5N1, but differ in 

a number of ways. In this longer, more 

specific nomenclature for influenza A 

strains, the “A” refers to the influenza 

type; this is followed by the animal 

species from which the virus is isolated; 

the geographical location; a laboratory 

strain designation; the year of isolation; 

and then the abbreviated HA and NA 

subtype. Previous exposure to and/or 

vaccination with the same subtypes that 

have genetic drift differences, confers 

only partial protection against the virus. 

For example, in the U.S. during 2004–

2005, the flu vaccine contained the 

H3N2 strain A/human/Fujian/411/2002 

(H3N2), but individuals may want to be 

vaccinated with the 2005–2006 vaccine, 

containing A/human/California/7/2004 

(H3N2), as the virus that is in 

circulation has undergone genetic drifts 

over time. Similarly, in birds, the H5N1 

strain originally identified in Hong 

Kong in 1997 was highly pathogenic to 

chickens, but was inefficient in infecting 

ducks. Whereas, the H5N1 strains isolated 

since 2002 are well-adapted to ducks; in 

fact, researchers have found that a number 

of different strains of H5N1 are now 

simultaneously circulating in Asia.

 Large-scale changes (genetic shifts) 

occur when the influenza A virus 

recombines with genetic material from 

two or more strains, leading to the 

emergence of influenza virus with a novel 

hemagglutinin subtype. The abrupt shift 

of hemagglutinin into a different subtype 

has led to pandemics, because there is no 

protective immunity in the population and 

the virus spreads rapidly from person to 

person across the globe. In the twentieth 

century, the world experienced three 

pandemics, H1N1 (1918–1919), H2N2 

(1957–1958), and H3N2 (1968–1969). 

Mammals, such as pigs, can serve as a 

“mixing vessel” between avian and human 

influenza viruses (Figure 1). Pigs can be 

infected with influenza viruses from both 

birds and people. If a pig is infected with 

both viruses at the same time, the two 

different viruses can recombine and give 

rise to new combinations that mix genetic 

materials and capabilities from the two 

parental viruses. 

The Asian H5N1 strain has created new 

flu-transmission scenarios. The virus is 

able to directly infect people who have 

contact with infected poultry. As of July 

2005, H5N1 has caused at least 109 

human cases, over half of them fatal, in 

five Asian countries. The current H5N1 

is primarily an avian 

virus, it is inefficiently 

transmitted to people 

and there is no evidence 

of sustained person-toperson transmission. The 

H5 hemagglutinin has not 

been widely circulated 

in humans, so people do 

not have cross-protective 

immunity. The concern 

is that if the H5N1 virus 

mutates or recombines with 

other strains of influenza 

A viruses, perhaps one 

that spreads from personto-person efficiently, the 

H5N1 virus may acquire such abilities 

and evolve to become the next pandemic 

strain. 

Currently, the implications of HPAI 

H5N1 for North American wildlife 

remain unclear. If migratory birds carry 

and shed the virus along flyways, the 

potential exists for the virus to spread 

into additional migratory species and for 

the subsequent spread of the H5N1 virus 

into other parts of the world including 

Europe, Australia, and North America. 

It is unclear whether infected birds are 

capable of migration, and carrying and 

shedding the virus.

Bird migration is only one of the 

possible routes of introducing HPAI 

H5N1 to the North American continent. 

Travel by infected people, along with 

contaminated luggage or clothing, 

and transportation of infected poultry, 

including the smuggling of illegal pet 

birds, and other poultry equipment 

and products, are more direct means to 

transport the virus.

The USGS National Wildlife Health 

Center (NWHC) has the capability to 

detect HPAI H5N1 and is screening 

select submissions for avian influenza. 

The availability of molecular technology 

has enabled NWHC to test for the 

influenza viruses that carry the H5, H7 

(another possible poultry pathogen) 

and N1 subtypes. The NWHC, with 

assistance from others, has begun 

to conduct targeted surveillance of 

aquatic birds for avian influenza 

and will continue to assist in disease 

investigations of wildlife mortality 

events. Also planned are experimental 

studies in wild waterfowl and other 

waterbirds to better understand the 

potential role of, and impact to, various 

North American waterbird species.

For additional information, please contact 

Hon Ip (608-270-2464) or Paul Slota 

(608-270-2420) at the 

USGS National Wildlife Health Center

6006 Schroeder Road

Madison, WI 53711

http://www.nwhc.usgs.gov Chickens infected with H5N1. Note flaccid combs and the depressed 

and lethargic appearance of the lower chicken.

Photo courtesy of Ilaria Capua