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Avian influenza: The animal health perspective (Part 2)
Highly pathogenic avian influenza, previously known as fowl plague, is regarded as the most infectious and devastating disease of poultry. It was one of the very first animal diseases included in List A of the World Organization for Animal Health — namely diseases with potential for rapid interboundary spread and severe implications for international trade.
Notably, highly pathogenic avian influenza (HPAI) has become zoonotic during the last decade.
In the first part of the review published in the May issue, we addressed the terms notifiable avian influenza, low pathogenicity avian influenza and HPAI and underlined the fact that — to date — only avian influenza virus subtypes containing H5 or H7 have been found to be highly pathogenic.
The second part of this Infectious Disease News review includes a brief discussion of epidemiological aspects of HPAI in avian species, describes some of the clinical and pathological characteristics and addresses some of the methods applied for HPAI identification.
Epidemiology
In birds, avian influenza viruses are shed in the feces as well as in saliva and nasal secretions. Fecal–oral transmission is usually the predominant means of spread in wild bird reservoirs. However, some recent isolates of H5N1 have been found in higher quantities in tracheal samples than feces, suggesting that the primary means of transmission for this virus may no longer be the fecal–oral route in some species. Once an avian influenza virus has entered a poultry flock, it can spread on the farm by both the fecal–oral route and aerosols, due to the close proximity of the birds. Fomites are important in transmission, and flies may act as mechanical vectors. Avian influenza viruses can persist in some environments for weeks and have been isolated from the water in ponds where ducks swim.
In countries where HPAI has been eradicated from domesticated poultry, the disease can be introduced into flocks by migratory waterfowl as well as infected poultry or fomites. Until recently, wild birds were thought to carry only the low pathogenic form of avian influenza viruses. Once they were introduced into poultry, these viruses recombined or mutated to produce HPAI viruses. However, some migratory waterfowl appear to carry and disseminate the currently circulating, highly pathogenic H5N1 strains. Whether these birds can migrate long distances after being infected is controversial. The recent (April/May 2008) H5N1 epizootic in South Korea’s poultry farms and, almost simultaneously, cases in wild swans in Japan shown to be caused by the same strain, may be seen as supportive of the accumulating evidence that the migrating and wild birds route should not be ignored. According to the data collected by the U.S. Geological Survey, at least 108 species of wild birds, belonging to 14 orders, have reportedly been found to be infected by H5N1 as of May 2008. The largest group (35 species) belongs to the order Anseriformes (waterfowl, including ducks, geese, swans and screamers).
Some avian influenza virus strains can also be transmitted to mammals by direct or indirect contact. Close contact with dead or sick birds seems to be the principal means of transmission to humans; however, a few cases may have resulted from exposure to contaminated feces, and swimming in contaminated water is theoretically a source of exposure. Transmission by ingestion has been reported rarely in humans, felines and dogs. Two people became infected with an H5N1 virus after eating uncooked duck blood. One H5N1 infection occurred in a dog that had eaten infected duck carcasses. Similarly, leopards and tigers in zoos, as well as housecats, were probably infected with H5N1 when they ate raw birds. Experimental infections have been established in cats by intratracheal inoculation with H5N1 viruses and by feeding them H5N1–infected chicks. Dogs were infected by intratracheal inoculation combined with intranasal inoculation.
Cats appear to shed the virus from the intestinal tract as well as the respiratory tract.
Limited animal-to-animal transmission appears to have occurred in zoo tigers, as well as in experimentally infected housecats in some studies. No animal-to-animal transmission was reported in the asymptomatic cats infected by exposure to a sick swan or in experimentally infected pigs.
Clinical signs
The clinical signs of avian influenza infection are variable and influenced greatly by the virulence of the viruses involved, the species infected, age, concurrent viral or bacterial disease and the environment. The virulence exhibited in chickens can vary during an outbreak. There are nonpathogenic viruses (no clinical signs in infected birds, with seroconversion), low or mild pathogenic viruses (clinical signs in chickens and turkeys range from inapparent to mild or severe respiratory disease and can be confused with other poultry respiratory diseases) and highly pathogenic viruses.
The incubation period is highly variable and ranges from a few days to one week. HPAI viruses may cause, in the most extreme form, peracute cases involving sudden death practically without clinical signs, when mortalities occur within hours after onset of depression. Overall mortality rates for peracute/acute cases nearing 100% have been reported.
In acute cases, mortalities occur as early as 24 hours after the first signs of the disease and frequently within 48 hours. In other cases, more diverse visible signs are seen, and mortalities can be delayed for as long as a week.
Clinical signs in chickens and turkeys depend on the age and type of bird and on environmental factors. Signs include severe respiratory distress with excessively watery eyes and sinusitis, edema of the head and eyelids, diarrhea and nervous signs. Some severely affected hens may recover but rarely come back into lay.
The disease in turkeys is similar to that in chickens but is often complicated by secondary infections.
Gross pathology
In many cases, poultry dying from the peracute form of the disease lack visible gross pathological lesions. With acute infections in chickens, there is severe lung congestion, hemorrhage and edema; other organs and tissues appear normal. More varied visible lesions are seen in chickens surviving three to five days.
Internally, the characteristics of acute infections with viruses causing HPAI are hemorrhagic, necrotic, congestive and transudative changes.
As the disease progresses, and in cases due to mild pathogenic avian influenza viruses, lesions may be seen in the sinuses characterized by catarrhal, serofibrinous, mucopurulent or caseous inflammation, and the tracheal mucosa may be edematous with exudates varying from serous to caseous.
Histopathological lesions seen in the gross changes are not definitive for HPAI, although vasculitis in the brain and other organs may be highly suggestive of the disease. Diagnosis of the disease therefore depends on the isolation of the virus, its characterization and the demonstration that it fulfills one of the criteria recognized internationally as typical of HPAI.
Diagnosis
Until recently, virus isolation has been performed by the inoculation of embryonated fowls eggs by suspensions made of tracheal and cloacal swabs (or feces) taken from live birds or of feces and pooled samples of organs from dead birds. Following an incubation for four to seven days, the eggs are tested for the presence of hemagglutinating activity. The presence of influenza A virus can be confirmed by an immunodiffusion test. Isolation in embryos has recently been replaced, under certain circumstances, by reverse transcription polymerase chain reaction.
For subtyping the virus, the laboratory must have monospecific antisera prepared against the isolated antigens of each of the 16 hemagglutinin (H1–H16) and nine neuraminidase (N1–N9) subtypes of influenza A viruses that can be used in immunodiffusion tests. Alternatively, the newly isolated virus may be examined by hemagglutination and neuraminidase inhibition tests against a battery of polyclonal antisera to a wide range of strains covering all the subtypes.
As the terms “highly pathogenic avian influenza” and “fowl plague” refer to infection with virulent strains of influenza A virus, it is necessary to assess the virulence of an isolate for domestic poultry. The methods used for the determination of strain virulence for birds have evolved during recent years with a greater understanding of the molecular basis of pathogenicity but still primarily involve the inoculation of a minimum of eight susceptible 4- to 8-week-old chickens with infectious virus. Strains are considered to be highly pathogenic if they cause greater than 75% mortality within 10 days or have an intravenous pathogenicity index of greater than 1.2.
The role of basic amino acids adjacent to the cleavage site of the hemagglutinin protein is well known and is a diagnostic feature for the HPAI profiling in poultry, in particular for the evaluation of the pathogenicity rate of the isolate.
Characterization of suspected virulent strains of the virus should be conducted in a virus-secure laboratory.
The World Organization for Animal Health (OIE)’s guidelines for the notification of suspected or confirmed HPAI outbreaks and recommended measures to be applied for the prevention, control or eradication of the disease in animals will be the subject of our next column. We shall also touch upon internationally binding rules for the certification to accompany interstate-traded consignments of fowl and poultry products.
For more information:
- Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases and Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.
- OIE’s manual of standards for diagnostic tests and vaccines is available online at http://oie.int/eng/normes/mmanual/A_00037.htm.