Avian influenza: The animal health perspective

On Aug. 22, 1997, ProMED posted the following e-mail, received from John S. Tam, PhD, at the department of microbiology at the Chinese University of Hong Kong:

“It had been brought to my attention that you were asking for information concerning the H5N1 isolate of influenza A virus in Hong Kong. … The Department of Health of Hong Kong Government announced that a 3-year-old boy was diagnosed to be infected with an influenza A virus of the H5N1 serotype (avian influenza strain). The boy subsequently died of complications of pneumonia and possible Reye’s syndrome in May of this year. The virus was isolated by the Hong Kong Government Department of Health virus laboratory and found to be not the current circulating influenza viruses in Hong Kong (H3N2 and H1N1). With the help of WHO reference laboratories and other independent influenza virus researchers in Europe, the virus was identified to be an influenza A virus with serotype H5N1. The patient was a resident of Hong Kong and not from mainland China as reported. There had been no subsequent influenza A virus serotype H5N1 isolates identified so far, and there is no increased influenza activity locally.”

This e-mail was followed by ProMED-mail moderator Jack Woodall’s commentary:

“Thanks, John, for a yet more authoritative report on the subject. Now we need someone to tell us what this means in terms of influenza epidemiology. Should the world be increasing flu surveillance, preparing a vaccine?”

Link to animals

During the 1997 Hong Kong outbreak, 17 additional human patients, five of whom died, were recorded. The source of their infection was ducks or chickens. The epizootic was effectively eradicated by the local veterinary authorities, applying drastic measures to eliminate infected fowl. The possibility that infection continued simmering in adjacent territories cannot be excluded.

Avian influenza viruses are found in a wide variety of domestic and wild birds. They are also isolated occasionally from mammals. In 1997, there was only one previous record of the virus crossing the animal/human species barrier; in 1996, an avian H7 influenza virus was isolated in England from a woman with conjunctivitis. The source of the virus was considered to be waterfowl, since she tended a collection of 26 ducks of various breeds that mixed freely with feral waterfowl on a small lake. Previously, avian influenza viruses were known not to replicate efficiently in humans, indicating that direct transmission of avian viruses to humans would be a rare event. For example, high doses of avian influenza viruses were required to produce a quantifiable level of replication in human volunteers. During the 1983 to 1984 Pennsylvania H5N2 outbreak in poultry, no cases of influenza-like illness were reported among workers exposed to highly pathogenic avian viruses.

In mid-February 2003, the H5N1 strain reemerged again in Hong Kong, infecting two people (one of whom died). Two months later on April 17, 2003, a 57-year-old veterinarian who visited a poultry farm affected by the H7N7 strain died of acute respiratory distress syndrome in the Netherlands. H7N7 influenza virus was isolated from the patient. No other respiratory pathogen was detected in a series of laboratory tests. More than 80 additional H7N7 mild cases were confirmed in humans by the Dutch health authorities; all were infected from birds.

Global spread

The 2003 cases have become forerunners of a global epizootic, which spread dramatically during the following years. As of April 23, 2008, 48 countries in Asia, Africa and Europe have been infected since 2003, according to data from the World Organization for Animal Health (OIE). The outbreaks have included 6,245 in domestic fowl, predominantly chickens, ducks, geese and turkeys. Of the said outbreaks, 74.9% have been reported from three countries: Vietnam (2,475), Thailand (1,139) and Egypt (1,065). As of April 17, 2008, human infections have been reported from 14 of the highly pathogenic avian influenza (HPAI)-affected countries, with 381 cases and 240 deaths.

In May 2008, HPAI will complete its 11th year as a zoonosis, a title it had never acquired before. Fowl plague — as the disease was named for more than one hundred years — was always 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 OIE, namely diseases with potential for rapid international spread. This review is meant to address mainly animal-health aspects of the disease.

Fowl plague was first described in 1878 as a disease affecting chickens in Italy. The causative agent was eventually isolated from a chicken in 1902, marking the first documented isolation of influenza virus. Similar outbreaks were observed in Europe and then worldwide, with subsequent isolation of several fowl plague viruses. By contrast, the first human influenza virus was not isolated until 1933.

In 1981, the term fowl plague, as well as its parallels in other languages, such as the German and Dutch “vogelpest” and the French “peste aviaire”, were abandoned for the more accurate term HPAI.

Avian influenza is caused by specified viruses that are members of the family Orthomyxoviridae and placed in the genus Influenza virus A. There are three influenza genera: A, B and C; only influenza A viruses are known to infect birds. Infections in birds can give rise to a wide variety of clinical signs that may vary according to the host, strain of virus, the host’s immune status, presence of any secondary exacerbating organisms and environmental conditions. These viruses are highly contagious and extremely variable, particularly widespread in wild waterfowl and shore birds. Most of them are usually carried asymptomatically by wild birds and cause only mild disease in poultry, known as low pathogenicity avian influenza (LPAI). Other strains demonstrate high pathogenicity and may cause fowl plagues, killing up to 90% to 100% of a poultry flock. Such cases have been seen in recent years also in wild birds but are regarded exceptional. Epidemics of HPAI can spread rapidly, devastate the poultry industry and result in severe trade restrictions.

Two surface antigens, the hemagglutinin and neuraminidase proteins, are used to classify type A influenza viruses into subtypes. There are 16 hemagglutinin antigens (H1 to H16) and nine neuraminidase antigens (N1 to N9). Waterfowl and shore birds, which seem to be the natural reservoirs for the type A influenza viruses, carry all of the known hemagglutinin and neuraminidase antigens and therefore all of the subtypes. The predominant subtypes in wild waterfowl change periodically.

To date, only subtypes containing H5 or H7 have been found to be highly pathogenic; subtypes that contained other hemagglutinins have been found only in the LPAI form.

Classification

During the recent years, all H5 and H7 viruses have been classified by the OIE as notifiable avian influenza (NAI) viruses, independently of their pathogenicity rate. This is due to the risk of low pathogenic H5 or H7 becoming virulent by mutation in poultry hosts. Although all virulent strains isolated to date have been of the H5 or H7 subtype, most H5 or H7 isolates have been of low virulence.

Any of the other 14 hemagglutinin subtypes found to have high pathogenicity will be regarded as an NAI virus.

The methods used for the determination of strain virulence for birds have evolved during recent years, leading to better understanding of the molecular basis of avian influenza pathogenicity. The traditional method involved a bioassay in chickens to determine an intravenous pathogenicity index. The obtained results of the bioassay or, alternatively, of recognized novel molecular procedures, will enable the determination of H5 or H7 isolates as highly pathogenic notifiable avian influenza or low pathogenicity notifiable avian influenza viruses. Non-H5 or non-H7 avian influenza isolates that are not highly pathogenic for chickens are identified as LPAI and are not notifiable.

Some clinical, pathological and epidemiological aspects of HPAI in fowl; internationally obliging requirements for HPAI identification, notification, prevention and control/eradication; and for the certification of safe international trade in fowl and poultry products will be addressed in next month’s column.

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.
• Beare AS, Webster RG. Replication of avian influenza viruses in humans. Arch Virol. 1991;119:37-42.