Resurgence of HPAI in Birds and Mechanisms of Transmission
David E. Swayne, MSc, DVM, PhD, dACVP, dACPV
Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of
Agriculture, Athens, Georgia 30605 USA
David.Swayne@ars.usda.gov
1. Summary
High pathogenicity avian influenza (HPAI) viruses typically produce a severe, systemic disease
with high mortality in chickens and other gallinaceous birds, but either no disease or only mild
disease in domestic ducks and wild birds. However with emergency of H5N1 HPAI viruses and
their maintenance in domestic poultry for past 17 years, there has been a shift in virulence within
chickens evident as shorter means death times (MDT) and widespread virus replication in
vascular endothelial cells. In domestic ducks, H5N1 HPAI viruses have changed from producing
inconsistent respiratory infections in 2 week-old domestic ducks to some strains being highly
lethal in adult ducks with virus in multiple internal organs and the brain.
The H5N1 HPAI virus has crossed multiple species barriers to infect domestic poultry, captive
and wild birds, carnivorous mammals and humans. Human infections have been associated with
direct or indirect contact with live or dead poultry while in carnivores, consumption of infected
birds or their products have been associated with infections. Experimental studies in the ferrets
and pigs demonstrated transmission of H5N1 HPAI virus by oral or direct digestive tract
exposure, but required a much higher dose of virus than exposure via the upper respiratory tract.
With respiratory trophic H5N1 virus, consumption of infected meat by ferrets initiated infection
through the tonsil followed by nasal cavity, but with systemic H5N1 HPAI viruses simultaneous
infection also occurred via the upper digestive tract with spread to liver and pancreas. Slaughter
of H5N1 HPAI virus infected asymptomatic chickens, produced airborne virus in large droplets
and aerosols, and transmitted the virus to infect and kill chickens and ferrets exposed within the
same air-space.
2. Introduction
Avian influenza (AI) viruses are a diverse group of type A orthomyxoviruses divided into 144
different subtypes based on different combinations of the 16 hemagglutinin and 9 neuraminidase
subtypes, and two different pathotypes (low [LP] and high pathogenicity [HP]). LPAI can be any
of the 16 H subtypes, but only H5 and H7 subtypes have been HPAI viruses.
3. Pathology
In gallinaceous poultry, infection by LPAI viruses produces lesions of inflammation principally
in then respiratory tract, especially the upper respiratory tract. However, LPAI viruses can
replicate in the intestinal tract but typically without lesions. By contrast, HPAI viruses produce
systemic infection in gallinaceous poultry with associated lesions of necrosis and inflammation
in most organ systems.
However, the HPAI viruses usually produce no clinical signs of infection or only mild disease in
domestic ducks and wild birds. Over the past decade, the emergent HPAI viruses have shifted to
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increased virulence for chickens as evident by shorter mean death times (MDT) and a greater
propensity for massive disseminated replication in vascular endothelial cells. Especially
important, the Asian H5N1 HPAI viruses have changed from producing inconsistent respiratory
infections in 2 week-old domestic ducks to some strains being highly lethal in ducks with virus
in multiple internal organs and brain. However, the high lethality for ducks is inversely related to
age, unlike these viruses in gallinaceous poultry which are highly lethal irrespective of the host
age. The most recent Asian H5N1 HPAI viruses have infected some wild birds producing
systemic infections and death. Across all bird species, the ability to produce severe disease and
death is associated with high virus replication titers in the host, especially in specific tissues such
as brain and heart
4. Field Situation
There have been 35 epizootics of high pathogenicity avian influenza (HPAI) in birds since 1959.
The H5N1 (HPAI) virus emerged in China during 1996 and has spread to infect poultry and/or
wild birds in 63 countries during the past 18 years. In the past 2 years, the majority of the
outbreaks of H5N1 HPAI have occurred in Indonesia, Egypt, Vietnam, and Bangladesh, in
decreasing order, but also limited cases have been reported in Bhutan, Cambodia, Hong Kong,
India, Laos, Libya, North Korea, Myanmar, and Nepal. The majority of the HPAI cases have
been H5N1, but outbreaks of H5N2 have occurred in Chinese Taipei (chickens) and South Africa
(ostriches), an outbreak of H7N3 HPAI in Mexico (egg-type chickens), an outbreak of H7N7
HPAI in Australia (free range layers), an outbreak of H7N2 HPAI in Australia (free range
chickens and layers), and an outbreak of H7N7 in Italy (layers). Reassortment of the
hemagglutinin gene of the H5N1 HPAI within China has resulted in emergence of viruses with
changes in internals gene segments and different neuraminidases; i.e. H5N2, H5N5, H5N6 and
H5N8. The latter has caused outbreaks in South Korea (breeder and meat ducks) and Japan.
5. Transmission
Several of the AI viruses have crossed multiple species barriers to infect various poultry species,
captive and wild birds, carnivorous mammals and humans.
4.1 Transmission between poultry.
In a series of studies,1 an H5N1 HPAI virus (A/Whooper Swan/224/05) was used to determine
the susceptibility and pathogenesis of chickens and domestic ducks when administered through
respiratory or alimentary routes of exposure. The chickens and ducks were more susceptible to
the H5N1 HPAI virus, as evidenced by low infectious and lethal viral doses, when exposed by
intranasal as compared to alimentary routes of inoculation (intragastric or oral fed). In the
alimentary exposure pathogenesis study, pathological changes included hemorrhage, necrosis
and inflammation in association with virus detection were generally observed in most visceral
organs of chickens between 2 and 4 DPI, which is similar to lesions and virus localization in
birds exposed by natural or experimental intranasal routes. Similarly, the virus caused systemic
infection in the ducks characterized by moderate lymphocytic encephalitis, necrotized hepatitis
and pancreatitis with corresponded demonstration of virus. However, with alimentary exposure,
lesions and/or virus was first demonstrated in upper alimentary tract on 1 DPI suggesting
alimentary tract was initial site affected upon consumption of infected meat or gavage of virus in
liquid medium. Alimentary infection does require higher exposure doses to produce infection
when compared to intranasal exposure in chickens. These data suggest that respiratory exposure
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to H5N1 HPAI virus in birds is more likely to result in virus transmission than consumption of
infected meat unless the latter contain high doses of virus such as in cannibalized infected
carcasses.
Transmission Birds to Mammals, including Humans.
With carnivores, consumption of infected birds or their products have been associated with
infections. Consumption of infected meat by ferrets resulted in respiratory system infection with
A/Muscovy duck/Vietnam/209/05 and A/Whooper swan/Mongolia/244/05 viruses, or in both
severe respiratory and systemic infection with predominant involvement of the liver, pancreas,
and large and small intestine with A/Vietnam/1203/04 virus.2 Direct intragastric exposure to
infected meat (A/Vietnam/1203/04 virus) resulted in lethal systemic disease mainly affecting the
intestine, liver, and pancreas but not involving the lungs. These results demonstrated that
exposure of the digestive system to H5N1 influenza viruses could initiate infection either
through the tonsil, with spread to respiratory tissues, or through intestinal infection, with spread
to the liver and pancreas. Additional work looking at non-Asia HPAI viruses, the dose of virus
needed to infect ferrets through consumption was much higher than via respiratory exposure and
varied with the virus strain.3 In addition, H5N1 HPAI viruses produced higher titers in the meat
of infected chickens and more easily infected ferrets than the H7N3 or H7N7 HPAI viruses.
The majority of human infections with H5N1 high pathogenicity avian influenza (HPAI) virus
have occurred in the village setting of developing countries with the primary exposure risk being
direct contact with live or dead poultry in the household or neighborhood. In Egypt, the majority
of the human H5N1 HPAI virus infections with clinical disease have been in women and
children and they are the high risk group who tend, play with, slaughter and prepare the
household poultry for consumption. Halal slaughter of poultry requires free movement of the
bird during the death struggle, which tends to create a viral plume thereby enhancing human
exposure by inhalation.
In experimental studies in BSL-3Ag, simulated home slaughter of asymptomatic H5N1 HPAI
virus infected chickens in generated airborne virus, and chickens and ferrets housed in same
airspace as the slaughter process became infected and died.4 Conducting the slaughter step of
H5N1 HPAI virus-infected non-vaccinated chickens in a plastic bag greatly reduced the virus
transmission through the air to ferrets.
Experimental ferret models have shown airborne transmission of the virus from simulated
slaughter of subclinically infected chickens or through feeding infected meat. However, the
infectious dose required in much lower with aerosol exposure.
6. References
1. Kwon YK, Swayne DE: Different routes of inoculation impact infectivity and pathogenesis
of H5N1 high pathogenicity avian influenza virus infection in chickens and domestic
ducks. Avian Dis 54(4):1260-1269, 2010
2. Lipatov AS, Kwon YK, Jackwood MJP, Swayne DE: Pathogenesis of H5N1 influenza
virus infections in mice and ferret models differ between respiratory and digestive system
exposure . J Infect Dis 199:717–25, 2009.
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3. Bertran K, Swayne DE: High doses of highly pathogenic avian influenza virus in chicken
meat are required to infect ferrets. Vet Res 45:60, 2014
4. Swayne DE. Mechanisms of transmission and spread of H5N1 high pathogenicity avian
influenza virus in birds and mammals. Abstracts of the Seventh International Symposium
on Avian Influenza, pp 50-51. 2009.
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