Definition
Avian influenza (AI) is a disease of viral etiology that ranges
from a mild or even asymptomatic infection to an acute, fatal disease of chickens,
turkeys, guinea fowls, and other avian species, especially migratory waterfowl
(1,2,3,4,8,9,10,11).
Etiology
Fowl plague was described in 1878 as a serious disease of chickens
in Italy. It was determined in 1955 that fowl plague (FP) virus is actually one of the
influenza viruses. The AI viruses, along with the other influenza viruses, make up the
virus family Orthomyxoviridae. The virus particle has an envelope with glycoprotein
projections with hemagglutinating and neuraminidase activity. These two surface antigens,
hemagglutinin (HA) and neuraminidase (NA), are the basis of describing the serologic
identity of the influenza viruses using the letters H and N with the appropriate numbers
in the virus designation e.g., H7N2. There are now 15 hemagglutinin and 9 neuraminidase
antigens described among the Type A influenza viruses. The type designation (A, B, or C)
is based upon the antigenic character of the M protein of the virus envelope and the
nucleoprotein within the virus particle. All influenza viruses affecting domestic animals
(equine, swine, avian) belong to Type A, and Type A influenza virus is the most common
type producing serious epidemics in humans. Types B and C do not affect domestic animals.
Classical fowl plague viruses have H7 as one of the surface
antigens but can have different N antigens. It was once believed that all H7 viruses are
highly pathogenic fowl plague viruses and that no other avian influenza viruses could
produce a fowl-plague-like disease. When avirulent AI viruses with the H7 antigens were
demonstrated in turkeys in 1971 and highly virulent AI viruses with the H5 antigen were
first found in chickens in 1959, the necessity for redefining the term fowl plague or
using other terminology became apparent. Because there are highly virulent AI viruses that
possess H antigen other than the H7 and H7 AI viruses that do not produce clinical fowl
plague, an international assembly of avian influenza specialists proposed that the term
fowl plague no longer be used. They suggested that any AI virus, regardless of its HA
designation, meeting specified virulence requirements in the laboratory be designated
highly pathogenic avian influenza (HPAI). The criteria that serve as the basis for
classifying an AI virus as HPAI has more recently been modified to include molecular
considerations such as the type of amino acids at the cleavage site of its HA. This
chapter will be limited to describing the HPAI and not the AI viruses of less virulence
and pathogenicity.
Host Range
Most avian species appear to be susceptible to at least some of
the AI viruses. A particular isolate may produce severe disease in turkeys but not in
chickens or any other avian species. Therefore, it would be impossible to generalize on
the host range for HPAI, for it will likely vary with the isolate. This assumption is
supported by reports of farm outbreaks where only a single avian species of several
species present on the farm became infected. Swine appear to be important in the
epidemiology of infection of turkeys with swine influenza virus when they are in close
proximity. Other mammals do not appear to be involved in the epidemiology of HPAI. The
infection of humans with an H5 avian influenza virus in Hong Hong in 1997 has resulted in
a reconsideration of the role of the avian species in the epidemiology of human influenza.
Geographic Distribution
Highy pathogenic avian influenza viruses have periodically
occurred in recent years in Australia (H7), England (H7), South Africa (H5), Scotland
(H5), Ireland (H5), Mexico (H5), Pakistan (H7), and the United States (H5). Because
laboratory facilities are not readily available in some parts of the world to
differentiate Newcastle disease and HPAI, the actual incidence of HPAI in the world's
poultry flocks is difficult to define. It can occur in any country, regardless of disease
control measures, probably because of its prevalence in wild migratory waterfowl, sea
birds and shore birds.
Avian influenza has produced losses of variable severity,
primarily in turkeys in the United States, since the mid-1960's. The disease outbreaks in
turkeys in the United States have been caused by AI viruses with many of the HA
designations. It was in the fall of 1983 that a highly virulent H5 virus produced severe
clinical disease and high mortality in chickens, turkeys, and guinea fowl in Pennsylvania.
This severe disease, clinically indistinguishable from classical fowl plague, occurred
after a serologically identical but apparently mild virus had been circulating in poultry
in the area for 6 months.
Outbreaks of less virulent AI have frequently been described in
domestic ducks in many areas of the world. The AI viruses are often recovered from
apparently healthy migratory waterfowl, shore birds, and sea birds worldwide. The
epidemiologic significance of these isolations relative to outbreaks in domestic poultry
has led to the generally accepted belief that waterfowl serve as the reservoir of
influenza viruses.
Transmissions
There is a considerable body of circumstantial evidence to support
the hypothesis that migratory waterfowl, sea birds, or shore birds are generally
responsible for introducing the virus into poultry. Once introduced into a flock, the
virus is spread from flock to flock by the usual methods involving the movement of
infected birds, contaminated equipment, egg flats, feed trucks, and service crews, to
mention a few. Preliminary trapping evidence indicates that garbage flies in the
Pennsylvania outbreak were sources of virus on the premises of the diseased flocks. Virus
may readily be isolated in large quantities from the feces and respiratory secretions of
infected birds. It is logical to assume, therefore, that because virus is present in body
secretions, transmission of the disease can take place through shared and contaminated
drinking water. Airborne transmission may occur if birds are in close proximity and with
appropriate air movement. Birds are readily infected via instillation of virus into the
conjunctival sac, nares, or the trachea. Preliminary field and laboratory evidence
indicates that virus can be recovered from the yolk and albumen of eggs laid by hens at
the height of the disease. The possibility of vertical transmission is unresolved;
however, it is unlikely infected embryos could survive and hatch. Attempts to hatch eggs
in disease isolation cabinets from a broiler breeder flock at the height of disease failed
to result in any AI-infected chickens. This does not mean that broken contaminated eggs
could not be the source of virus to infect chicks after they hatch in the same incubator.
The hatching of eggs from a diseased flock would likely be associated with considerable
risk.
Incubation Period
The incubation period is usually 3 to 7 days, depending upon the
isolate, the dose of inoculum, the species, and age of the bird.
Clinical Signs
Infections of HPAI result in marked depression with ruffled
feathers, inappetence, excessive thirst, cessation of egg production, and watery diarrhea.
Mature chickens frequently have swollen combs, wattles (Fig. 25), and edema surrounding the eyes. The combs are often
cyanotic at the tips and may have plasma or blood vesicles on the surface with dark areas
of ecchymotic hemorrhage and necrotic foci (Fig. 26). The last eggs laid, after the onset of illness, are
frequently without shells. The diarrhea begins as watery bright green and progresses to
almost totally white. Edema of the head, if present, is often accompanied by edema of the
neck. The conjunctivae are congested and swollen with occasional hemorrhage. The legs,
between the hocks and feet, may have areas of diffuse hemorrhage (Fig. 27). Respiratory signs can be a significant feature of the
disease, depending on the extent of tracheal involvement. Mucus accumulation can vary. It
is not unusual in caged layers for the disease to begin in a localized area of the house
and severely affect birds in only a few cages before it spreads to neighboring cages.
Death may occur within 24 hours of first signs of disease,
frequently within 48 hours, or be delayed for as long as a week. Some severely affected
hens may occasionally recover.
In broilers, the signs of disease are frequently less obvious with
severe depression, inappetence, and a marked increase in mortality being the first
abnormalities observed. Edema of the face and neck and neurologic signs such as
torticollis and ataxia may also be seen.
The disease in turkeys is similar to that seen in layers, but it
lasts 2 or 3 days longer and is occasionally accompanied by swollen sinuses.
In domestic ducks and geese the signs of depression, inappetence,
and diarrhea are similar to those in layers, though frequently with swollen sinuses.
Younger birds may exhibit neurologic signs.
Gross Lesions
Birds that die with the peracute disease and young birds may not
have significant gross lesions other than severe congestion of the musculature and
dehydration. In the less acute form, and in mature birds, significant gross lesions are
frequently observed. They may consist of subcutaneous edema of the head and neck area,
which is evident as the skin is reflected (Fig. 28). Fluid may exit the nares and oral cavity as the bird is
positioned for postmortem examination. The conjunctivae are severely congested—
occasionally with petechiation. The trachea may appear relatively normal except that the
lumen contains excessive mucous exudate. It may also be severely involved with hemorrhagic
tracheitis similar to that seen with infectious laryngotracheitis. When the bird is
opened, pinpoint petechial hemorrhages are frequently observed on the inside of the keel
as it is bent back. Very small petechia may cover the abdominal fat, serosal surfaces, and
peritoneum, which appears as if it were finely splattered with red paint. Kidneys are
severely congested and may occasionally be grossly plugged with white urate deposits in
the tubules.
In layers, the ovary may be hemorrhagic or degenerated with
darkened areas of necrosis. The peritoneal cavity is frequently filled with yolk from
ruptured ova, causing severe airsacculitis and peritonitis in birds that survive for 7 to
10 days.
Hemorrhages may be present on the mucosal surface of the
proventriculus — particularly at the juncture with the gizzard. The lining of the
gizzard peels easily and frequently reveals hemorrhages and erosions underneath. The
intestinal muscosa may have hemorrhagic areas — especially in the lymphoid foci such
as the cecal tonsils. The gross lesions are not distinctly different from those observed
with velogenic viscerotropic Newcastle disease (VVND). The lesions in turkeys and domestic
ducks are similar to those in chickens but may not be as marked.
Morbidity and Mortality
The prognosis for flocks infected with HPAI is poor. Morbidity and
mortality rates may be near 100 percent within 2 to 12 days after the first signs of
illness. Birds that survive are usually in poor condition and resume laying only after a
period of several weeks.
Diagnosis
Field Diagnosis
Highly pathogenic avian influenza is suspected with any flock
where sudden deaths follow severe depression, inappetence, and a drastic decline in egg
production. The presence of facial edema, swollen and cyanotic combs and wattles, and
petechial hemorrhages on internal membrane surfaces increases the likelihood that the
disease is HPAI. However, an absolute diagnosis is dependent upon the isolation and
identification of the causative virus. Commercially available type A influenza
antigen-capture enzyme linked immunosorbent assay kits designed for use in human influenza
have recently shown promise as a possible rapid diagnositic test for poultry.
Specimens for Laboratory
Specimens sent to the laboratory should be accompanied by a
history of clinical and gross lesions, including any information on recent additions to
the flock. Diagnosis depends upon the isolation and identification of the virus from
tracheal or cloacal swabs, feces, or from internal organs (5). Specimens should be
collected from several birds. It is not unusual for many of the submitted specimens to
fail to yield virus. Swabs are the most convenient way to transfer AI virus from tissues
or secretions of the suspect bird to brain and heart infusion broth or other cell culture
maintenance medium containing high levels of antibiotics. Dry swabs should be inserted
deeply to ensure obtaining ample epithelial tissue. Trachea, lung, spleen, cloaca, and
brain should be sampled. If large numbers of dead or live birds are to be sampled, cloacal
swabs from up to five birds can be pooled in the same tube of broth. An alternative
technique is to place 0.5 cm3 of each tissue into the broth. Blood for serum
should be collected from several birds. If the specimens can be delivered to a laboratory
within 24 hours, they should be placed on ice. If delivery will take longer, quickfreeze
the specimens and do not allow them to thaw during transit.
Laboratory Diagnosis
Nine to 11-day-old embryonated chicken eggs are inoculated with
swab or tissue specimens. Avian influenza virus will usually kill embryos within 48-72
hours. If the virus isolated is identified as a Type A influenza virus, through the AGP or
ELISA tests, it is then tested using a battery of specific antigens to identify its
serologic identity (HA and NA type).
Sera from infected chickens usually yield positive antibody tests
as early as 3 or 4 days after first signs of disease.
Differential Diagnosis
Highly pathogenic avian influenza is easily confused with VVND,
because the disease signs and postmortem lesions are similar, and may also be confused
with infectious laryngotracheitis and acute bacterial diseases such as fowl cholera and Escherichia
coli. However, in an area where AI is prevalent, such as during an outbreak, sound
presumptive diagnoses can be made by flock history, signs, and gross lesions.
Treatment
Amantadine hydrochloride has been licensed for use in humans to
treat influenza since 1966. The medication is effective in reducing the severity of
influenza Type A in humans. Experimental evidence indicated possible efficaciousness in
poultry when the drug was administered in drinking water to reduce disease losses, but
drug-resistant viruses quickly emerged, negating the initial beneficial effects. Thus, the
drug is not recommended for use in poultry.
Vaccination
Inactivated oil-emulsion vaccines, although fairly expensive, have
been demonstrated to be effective in reducing mortality, preventing disease, or both, in
chickens and turkeys (7). These vaccines may not, however, prevent infection in some
individual birds, which go on to shed virulent virus. More economical viable vaccines
prepared using naturally avirulent or attenuated strains have the disadvantage of the
possible creation of reassortant influenza viruses with unpredictable characteristics.
These reassortants could result when a single host bird is simultaneously infected with
both the vaccine and another AI virus. Owing to the segmented nature of the influenza
virus genome, a reassortment of genetic material can readily occur, creating new influenza
viruses. The basic drawback to any vaccine approach for the control of HPAI is the large
number of HA subtypes that can cause the disease. Because there is no cross-protection
among the 15 known HA subtypes, either a multivalent vaccine will be needed or vaccination
postponed until the prevalent disease-causing subtype in the area is identified. A
recombinant fowl pox virus vaccine containing the gene that codes for the production of
the H5 antigen has recently been licensed. The use of a recombinant insect virus
containing the gene for either the H5 or H7 antigen has been used to make these vaccine
proteins in insect cell cultures.
Control and Eradication
The practice of accepted sanitation and biosecurity procedures in
the rearing of poultry is of utmost importance. In areas where waterfowl, shore birds, or
sea birds are prevalent, the rearing of poultry on open range is incompatible with a sound
AI prevention program (12). Appropriate biosecurity practices should be applied, including
the control of human traffic and introduction of birds of unknown disease status into the
flock. Cleaning and disinfection procedures are the same as those recommended in the
chapter on velogenic Newcastle disease.
Public Health
The AI viruses are Type A influenza viruses, and the possibility
exists that they could be involved in the development, through genetic reassortment, of
new mammalian strains. An influenza virus isolated from harbor seals that died of
pneumonia had the HA and NA surface antigens of an influenza virus isolated from turkeys a
decade earlier. The infection and deaths of 6 of 18 humans infected with an H5 avian
influenza virus in Hong Hong in 1997 has resulted in a reconsideration of the portentous
role that the avian species have on the epidemiology of human influezna. Previously there
was only one report of a human becoming infected with an H7 AI virus. Is is impossible to
predict the importance of AI virus in determining the strains of virus that infect humans.
There was no evidence to indicate that humans coming in contact with large quantities of
the H5N2 virus during depopulation efforts in the HPAI outbreak of 1983 in Pennsylvania
became infected with the virus.
GUIDE TO THE LITERATURE
1. ALEXANDER, D.J. 1982. Avian Influenza -Recent developments.
Vet. Bull., 52: 341-359.
2. Proceedings of the First International Symposium on Avian
Influenza, April 22-24, 1981, Beltsville, MD, R. A. Bankowski, Ed., Carter Printing
Co. Lib. Cong. Cat. Card No. 81-71692.
3. Proceedings Second International Symposium on Avian
Influenza. Sepember 3-5, 1986. Athens, GA, Richmond, VA: U.S. Animal Health Assoc.,
Lib. Cong. Cat. Card No. 86-051243.
4. Proceedings of the Third International Symposium on Avian
Influenza. May 27-29, 1992. Madison, WI, Richmond, VA: U.S. Animal Health Assoc., Lib.
Cong. Cat. Card No. 92-061298.
5. BEARD, C.W. 1989. Influenza. In A Laboratory Manual for the
Isolation and Identification of Avian Pathogens, 3d ed. H. G. Purchase et al., eds.,
Kennett Square, PA: American Association Avian Pathologists, pp. 110-113. Lib. Cong. Cat.
Card No. 89-80620
6. BEARD, C.W. 1989. Serologic Procedures. In A Laboratory
Manual for the Isolation and Identification of Avian Pathogens. 3d ed. H. G. Purchase
et al., eds., Kennett Square, PA: American Association Avian Pathologists, pp. 192-200.
Lib. Cong. Cat. Card No. 89-80620.
7. BRUGH, M., BEARD, C.W., and STONE, H.D. 1979. Immunization of
chickens and turkeys against avian influenza with monovalent and polyvalent oil emulsion
vaccines. Amer. J. Vet. Research, 40:165-169
8. EASTERDAY, B.C., and BEARD.W. 1984. Avian Influenza. Diseases
of Poultry, 8th ed. M. S. Hofstad et al., eds., Ames, IA: Iowa State University Press,
. pp. 482-496 .
9. EASTERDAY B.C., and HINSHAW,V.S. 1991. Influenza. In Diseases
of Poultry, 9th ed. B. W. Calnek et al,. eds., Ames, IA: Iowa State University Press,
pp. 532-551.
10. EASTERDAY, B.C., HINSHAW, V.S., and HALVORSON, D.A. 1997.
Influenza. In Diseases of Poultry, 10th ed., B.W. Calnek, et al, eds., Ames, IA:
Iowa State University Press, pp. 583-605.
11. EASTERDAY, B.C., and TUMOVA, B. 1978. Avian Influenza. In Diseases
of Poultry, 7th ed., M.S. Hofstad et al., eds., Ames, IA: Iowa State University Press.
12. HALVORSON, D.A., KARUNAKARAN, D., SENNE, D., KELLEHER, C.,
BAILEY, C., ABRAHAM, A., HINSHAW, V., and NEWMAN, J. 1983. Epizootiology of Avian
Influenza - - Simultaneous monitoring of sentinel ducks and turkeys in Minnesota. Avian
Dis., 27:77-85.
C.W. Beard, D.V.M., USDA, ARS. Southeast Poultry Research
Laboratory, Athens, GA.
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