Avian Influenza Virus

Over time the Avian Influenza virus (AIV) has shown to be a constant threat to rural livelihoods, avian production and human health, because it mutates very frequently and has a constant genetic movement. The recent events with different subtypes of Influenza virus like H5N1 or HINI pandemic in Asia, Europe, Middle East and Africa illustrate this (2).

AIV is an animal disease; veterinarians and vet scientists play an important role in the management in preventing humans coming into contact with the disease. We must resolve the problem of the carriers (wild and migrating birds) because they mobilize the virus, putting at risk commercial animals. The control and prevention of them are essential in avoiding a possible human pandemic (27, 28).

Influenza virus is divided into:

Types: A, B and C
Subtypes: H1 to H16 N1 to N9
Pathotypes: Low and High pathogenic (H5 and H7)
Genotypes: Clades (H5N1) (7).

Type A influenza viruses are segmented, negative sense RNA, enveloped viruses that can infect a wide variety of birds and mammals. However, the original reservoir of the influenza viruses is considered to be in wild waterfowl, gulls, and shorebirds (35).

The virus demonstrates a high degree of genetic variation, particularly in the hemagglutinin and neuraminidase genes, with 16 different hemagglutinin and 9 neuraminidase, subtypes being characterized from wild birds. Many of these hemagglutinin (HA) and neuraminidase (NA) subtypes have also been isolated from poultry, although chickens and turkeys are not considered a reservoir for avian influenza virus. Influenza is also common in some mammalian species, including swine, horses, and humans, but with only selected HA and NA subtypes, including H1N1 in swine, H3N8 in horses, and H1N1 and H3N2 in humans (21). Because of the propensity of influenza viruses to re-assort and to cross species, viruses with new combinations of genes can and do occur. For example, recent outbreaks of influenza in swine in North America have included not only the classic H1N1 viruses, but also H3N2 and H1N2 viruses (12, 40).

The Influenza virus, like other RNA viruses, lacks a “proofreading” mechanism, small errors that occur when the virus replicates are not corrected. As a result, their genetic composition constantly changes in small ways. These ongoing changes in the makeup of influenza A viruses are known as antigenic "drift." (25).

It is well documented that human influenza virus undergoes frequent antigenic drift, which is the accumulation of point mutations in the antigenic domain of the HA protein. As a result, viruses with a slightly changed antigenic structure emerge and can escape the host’s acquired immunity, whether this immunity is acquired by natural infection or vaccination.

Therefore, to maintain optimal protection by vaccination, the presently prevailing strains of influenza virus need to be included in each year’s influenza vaccine, requiring yearly reevaluation and frequent changes to the vaccine formulation Due to their eight segments of RNA, the virus can share their genes, between all the different subtypes of HA and NA, infecting the same cell, when viruses re-assort, a new hybrid virus is produced. This dramatic event is known as antigenic "shift." As human populations have no immunity to the resultant new virus, and as no existing vaccines can provide adequate protection, antigenic shift has historically resulted in pandemics that cause unusually severe diseases in large numbers of people. For this to occur, the new subtype must have genes from human influenza viruses that make it readily transmissible from human to human (8, 16, 32, 34).

The first outbreak of highly pathogenic AI was reported and described by Italian scientist Edoardo Perroncito in 1878. This is a groundbreaking report that describes the devastating and virulent disease as a contagious entity that affected poultry. The HPAIV etiology was not identified until 1901, by two Italian scientists who showed that "avian flu" could be reproduced in the laboratory by administering ultrafiltrates homogenized in ceramic filters, using organs obtained from dead birds affected by the disease.

Most AI viruses have been isolated from wild birds, particularly the water bird belonging to the orders Anseriformes and Charadriformes. These birds are apparently the natural reservoirs and in fact, function as stores of genes, which allow the perpetuation of AI virus in nature (9).

Unlike domestic birds, I mean the Order Galliformes, Phaisanidae family; they do not seem to be natural hosts of orthomyxovirus. Thus, the degree of host adaptation is low, which could possibly explain why documented viral mutations have almost always occurred in domestic poultry. In fact, the only outbreak of highly pathogenic AI in wild birds was reported in 1961 in South Africa when 1300 terns (Sterna hirundo) were affected and died (35).

Avian influenza can manifest itself with a variety of symptoms in chickens and turkeys, from a clinically unapparent infection to one with high mortality. The virus can generally be separated into viruses that primarily cause a mucosal or respiratory infection, referred to as lowpathogenicity avian influenza (LPAI). These viruses are more commonly isolated from poultry, and clinical signs generally range from asymptomatic infection to s in egg production and mild respiratory disease, although some low-pathogenic (LP) strains can cause higher mortality, usually due to coinfection with secondary pathogens (26). High pathogenicity avian influenza viruses cause high morbidity and high mortality, and it is an Office Internationale des Epizooties List A agent. HPAI is considered an exotic disease in the United States, and México. 

The OIE considered the H5 and H7 as an important subtype to chickens, which are uncommonly isolated from wild birds, often cause influenza outbreaks in chickens and turkeys in the United States. The reason for the apparent subtype discrepancy between the distribution of influenza in wild ducks and in poultry remains unknown (9).

Historically only H5 and H7 influenza viruses are associated with the highpathogenicity of avian influenza. Because of the heightened concern about H5 and H7 influenza viruses, representative isolates for these outbreaks were sequenced and compared to existing sequence databases to determine the relationships of each virus to others in the sequence database using phylogenetic analysis. This sequence analysis is also referred to as molecular epidemiology, and it provides the most precise way of determining the relationships of virus isolates to each other (29).

In the last ten years, there have been more than sixty outbreaks with High pathogenicity virus of avian influenza serotypes H5 and H7 affecting different animals and in different continents (America, Europe, Asia, Oceania and Africa), seven of them came from Low pathogenicity. (14, 22).

The countries in America continent that have recently been affected by low virus and / or highly pathogenic AI has been the United States in 1983-1984 HPAI virus H5N2, Mexico in 1994-1995 H5N2 HPAI virus, Chile in June 2002 virus HPAI H7N3, Canada in 2007 and 2008 HPAI H7N3 virus, LPAI virus Guatemala H5N2 in 2000 and El Salvador in 2001, the Dominican Republic LPAI virus in 2008 and Haiti in the same year (35).

In most of the outbreaks of HPAI, the affected chickens were culled; in addition to all the birds in a radius of 6 miles, this procedure, together with biosecurity measure, have contributed to control the diseases and in some countries Avian influenza has disappeared (Chile, Canada, USA etc) (34).

H7 AIV HIGH PATHOGENIC

H7N3, H7N7 and H7N1, these are the subtypes of AI, which have been recognized as causing severe outbreaks of influenza in different parts of the world, where they have affected broilers, layers, chickens, turkeys, ostriches, ducks, guinea fowls, quail, pheasant and backyard poultry (41).

The mutation rate, and for quantifying nucleotide changes in the hemagglutinin gene, estimated by using linear regression analysis, for the H7 isolates was 7.0 X10-3 nucleotide substitutions per site per year. This mutation rate is similar to mutation rates.

Previously described for H3 human influenza virus isolates 6.7 X 10-3 nucleotide substitutions per site per year and is higher than that reported for H3 equine influenza virus isolates. However, the estimated H7 AIV mutation rate is less than subtype H5.

Currently, an ongoing outbreak of H7 AIV has been observed since 1994, primarily in the live-bird markets (LBMs) in the Northeast United States (30). These LBMs, often catering to specific ethnic groups, provide a variety of live poultry, including chickens, turkeys, game birds, and ducks that can be slaughtered on site or sold live to the consumer. As part of an ongoing state and federal surveillance program, many different subtypes of AIV have been isolated from these LBMs.

H7N2 AI virus has been circulating in the northeast United States since 1994 and has been associated with at least five different outbreaks in industrialized poultry in seven states. The concern for LBMs in the introduction of AI virus has resulted in Hong Kong banning the sale of live ducks and geese in the markets, a comprehensive surveillance program, and stricter sanitary requirements. These changes have appeared effective in reducing the incidence of infected birds in the markets. An additional risk of introduction to commercial flocks and humans.

In March 2011, the H7N3 virus of low pathogenic AI was identified in 14, 000 turkeys to 19 weeks of age in the state of Missouri USA. The measures applied were Quarantine, Movement control inside the country, Vaccination prohibited, No treatment of affected animals (2).

Human´s Cases

In Netherlands in February 2003, de subtype H7N7 of AIV caused mild illness in 89 people and one Veterinarian died, in his lung the virus was isolated, this is the unique report of fatality in humans. 

In 2004, two poultry workers developed conjunctivitis and mild respiratory symptoms after an outbreak of an H7N3 HPAI in Canada.

The United Kingdom Health Protection Agency reports at least 4 human infections with low pathogenic avian influenza H7N2. 

The cases are associated with reported H7N2 Infections in poultry. 

Mammals reports

H7N7 was the only recognized influenza virus in horses until the early 1960s, when an H3N8 virus started to supplant the H7N7. In this case, the virus looked to be a completely new introduction of virus in the horse population. An H7N7 HPAI virus has caused infections without disease in pigs during the Dutch outbreak in 2003.

Vaccination Program

Just Italy and USA use vaccine in turkey (10, 33).

Current Situation

The final report with this subtype in poultry was in Guadalajara, Spain 2010, killing 30.000 die out of a flock of nearly 310,000 birds. All birds have now been culled (2).

H5N1

This subtype, have been causing enormous economic losses to chickens industry (broilers, layer chickens, duck, goose etc), due to, the high mortality, eradication measures, culling the affected flocks, quarantine disposition, biosecurity measures and restriction movements (domestic and international), trades control and the domestic and international health - sanitary barriers, have finished devastating the chicken economy of the affected countries, more than 300 millions of chickens culled or deaths.

H5N1 avian influenza is a public health concern because of its potential to spark a pandemic. As long as the virus continues to circulate in animals, there will be opportunities for this virus to infect and adapt to humans. Influenza viruses are usually host-specific. Avian influenza viruses, of which there are more than 100 identified combination of subtypes, normally only infect birds and in rare instances, pigs (pigs have receptors for all subtypes of avian viruses, likewise Quails).

Wild migratory birds are reservoirs for low pathogenic avian influenza (LPAI) viruses, but their role in transmitting highly pathogenic avian influenza (HPAI) viruses is hotly debated and unclear.

Such naturally resistant wild birds might serve as vectors for introduction of HPAI viruses into new locations. Data suggest that an HPAI virus may have been introduced into Egypt through a migratory bird. 

Studies of H5N1 viruses show that multiple genetically and antigenically distinct sub lineages of the virus are now established in poultry in parts of Asia. Poultry-to-poultry transmission is thought to sustain endemicity of the virus in this region. The H5N1 virus is isolated from apparently healthy migratory birds in southern China, suggesting that migratory birds can carry the virus over long distances.

The H5N1 subtype of Avian Influenza have emerged of the reassortment between the subtypes H9N2, (this, have been present since 1994 in quails in the South of China), as well as the H6N1 in teals and the H5N1 in goose. The vessel to this new virus was the quail, from this jump to the commercial chickens, and this to the humans (8).

The first documented human infections with H5N1 avian influenza occurred in 1997 in Hong Kong, when the virus caused severe respiratory disease in 18 humans, of whom six died. Rapid destructionwithin three days-of Hong Kong´s entire poultry population, estimated at around 1.5 million birds, reduced opportunities for further transmission to humans, and may have averted a pandemic (17).

Beginning in July 2005, a clade of HPAI (H5N1) viruses rapidly expanded from an apparent focus in western People´s Republic of China and spread to the Middle East, Africa, and Europe. Genetic analysis of HPAI virus isolates from dead wild birds along major flyways indicated that the strains were closely related to the Qinghai H5N1 A/bar-headed goose/Qinghai/65 /2005 virus (clade II).

Between 2005 and 2006 were the years where, most countries are reported in the presence of this highly pathogenic virus, with 56 affected countries. In 2011, the number ped significantly to only 6 (2).

Humans Cases

This subtype has caused fatalities in different age of human, from the youngest, 18 months, to the oldest, 70 yrs. 

The number of human´s fatalities of the virus, since its´reported presence until 2011, is 350. The most affected countries are as follows, Indonesia with 150, Egypt with 47, Vietnam with 63, China and China (Hong Kong SAR) with 28 and Thailand with 20.

A study describing the epidemiology of 54 human cases of H5N1 infection in Indonesia is published. Conclusions included that 76% of cases were associated with poultry contact, and the source of infection was not identified in 24% of cases Since 2005 to 2011, there have been just 9 human fatalities in Europe (Azerbaijan and Turkey) (7).

In addition to transmission to domestic poultry, HPAI (H5N1)-infected mute swans have been implicated in direct transmission to humans in Azerbaijan Two research groups have published findings that may help explain why the H5N1 virus does not easily infect humans or like normal seasonal influenza - spread readily by coughing or sneezing. Whereas human influenza viruses attach themselves to molecules in cells lining the nose and throat, avian viruses prefer to bind to molecules located deep in the lungs. Such findings are consistent with the clinical picture of H5N1 infection, in which most patients present with symptoms of infection in the lower respiratory tract, with rapid progression to pneumonia (4, 11).

CURRENT SITUATION:

AFRICA
Egypt A total of 39 H5 HPAI positive cases were reported in 11 governorates. Nearly 100,000 birds were culled. Of the 39 outbreaks, 27 were in backyard poultry (chickens, ducks, geese, turkeys) and 12 were in commercial chicken farms; and 8 outbreaks in commercial farms occurred even though they had been vaccinated. 

MIDDLE EAST
West Bank. An outbreak of H5N1 HPAI occurred in a turkey farm with 2,000 birds of 65-days old in Sealet al Harthieh, Jenin Governorate. Mortality reached 100 percent within three days, samples tested positive for H5N1 by PCR.

ASIA
Bangladesh A total of 55 H5N1 HPAI outbreaks occurred Most of the outbreaks were in commercial poultry farms with two outbreaks in backyard poultry. More than 170,000 birds died or were destroyed. Nearly 600 crows (Corvus spp.) were found dead in two places in Barisal Division (Amtali Upazilla and Patuakhali Sadar Upazila) and H5 avian influenza infection was confirmed by RT-PCR in samples taken from Patuakhali Sadar Upazila.

Cambodia A total of three cases of human H5N1 virus infection were reported in February 2011. 

China (Hong Kong SAR). A duck carcass found dead on a beach near Po Chue Tam India. H5 HPAI outbreak occurred in a government duck breeding farm in Agartala City, Tripura State on 3 February. A total of 2,198 out of 4,293 susceptible birds died, with the rest being culled. 

Indonesia The overall HPAI incidence was 1.9 infected villages per 1,000 villages under surveillance 

Japan H5N1 HPAI outbreaks were reported in 12 farms in 6 prefectures approximately 950,000 birds were destroyed. Meanwhile, 32 wild birds that were found weakened or dead in 11 prefectures include: great crested grebe (Podiceps cristatus), greater Scaup (Aythya marila), little grebe (Tachybaptus ruficollis), Mandarin duck (Aix galericulata), peregrine falcon (Falco peregrinus), tundra swan (Cygnus columbianus), whooper swan (Cygnus cygnus), grey heron (Ardea cinerea), hooded crane (Grus monacha), Ural owl (Strix uralensis) and crow (Corvus spp.). There were two outbreaks reported in captive birds, one of which occurred in a flock of swans in an amusement park. A total of 338 captive waterfowl were culled. 

Korea, the Republic of. A total of seven outbreaks of H5N1 HPAI were confirmed in poultry farms in two provinces Myanmar. Another H5 HPAI outbreak occurred in a layer chicken farm in Sagaing State on 20 February. A total of 626 out of 6,700 chickens died within five days. The rest were culled as a part of control measures.

Viet Nam. A total of eleven outbreaks in five provinces were reported in the north and the central regions, More than 12,700 birds were affected 

MAMMAL´S REPORTS 
A few HPAI viruses have caused infection and deaths in mammals including humans, but these viruses have not become established as endemic viruses and mammal-to-mammal transmission has been limited. Since 1997, the H5N1 HPAI virus has caused sporadic cases of infection and death in large felines (tigers and leopards), house cats, dogs, Owston´s palm civets, a stone martin, and domestic pigs, and a single case of H5N2 virus infection has been reported in pigs during the 1983-1984 outbreaks in the United States. Most of these H5N1 and H7N7 cases have involved close contact with infected birds or consumption of infected birds or their raw products. There are some cases of natural infections.

CONTROL AND ERADICATION
The best action for a country, zone or compartment in the control and prevention of AIV is the total eradication by slaughter of diseased animals´destruction of carcasses and all the elements related to infected birds (bed, food, etc.). Washing and disinfection of the barns and contaminated material according to the standards specified by the OIE in its Code of Animal Health Land, is another of the practices to be implemented In some countries, the characteristics of the poultry industry and the circumstances in which there have been outbreaks and epidemics caused by viruses of high and low pathogenicity AI, were forced to use the vaccination.
 
Vaccination is a useful tool for the control of avian influenza (AI) outbreaks, but its use is forbidden in most countries worldwide because of its interference with AI screening tests and its negative impact on poultry trade. Currently licensed AI vaccines increase host resistance to the disease but have a limited impact on the virus transmission. To control or eradicate the disease, a carefully conceived vaccination strategy must be accompanied by strict bio-security measure.

VACCINATION
Recently the Word Organization for Animal health (OIE), and the United Nation´s Food and Agricultural (FAO) have recommended the use of vaccination against H5N1 HPAI virus in developing countries where mass culling of poultry is no longer acceptable for ethical, cultural, ecological and economic reasons 

Countries vaccination
Thailand, China, Indonesia, Vietnam, Sudan and Egypt.

Type of vaccine:
Inactivated with mineral oil as Adjuvant it contained the whole virus: Some vaccine are including domestic strains and others labs, are using international strains (H5N2 and H5N9). This kind of vaccine is the most used.

Inactivated Recombinant vaccines:
Homologous vaccine, reverse genetic RG Live vaccine: Fowl pox and NDV as vectors 

Importance of the Vaccination
Vaccination in poultry in Indonesia helped reduce cases of death in the human population. Chickens immunized with a good level of humoral immunity, eliminate less virus when they have contact with the field virus, just as the birds become ill, require a greater amount of viral particles and the rate of morbidity and mortality is lower

H5N2
USAThe last two outbreaks of highly pathogenic virus has been commercial poultry in this country (Pennsylvania 83 and Texas 04), have come from low pathogenic virus (18, 24).

Avian influenza is a disease of economic importance, as shown in the outbreak of the highly pathogenic H5N2 subtype in North America. This outbreak occurred in domestic chickens and turkeys in Pennsylvania in .1983 - 84.With severe effects on the industry. The virus was eradicated by quarantine and depopulation of over 17 million birds at a direct economic loss, of over 60 million dollars. The indirect costs involved reestablishing the flocks and significantly increased prices for poultry products; they approached 350 million dollars. The American government covers a big part of this amount (3).

This country spends a substantial amount, which comes mostly from federal and state government in an ongoing campaign of epidemiological surveillance and monitoring of migratory birds, live bird market, slaughterhouses, storage facilities, farms etc. Which allows them to timely detect the presence of any subtype of influenza and take action immediately Health (31).

Despite extensive animal disease surveillance system which this country has, there is the possibility that there will be a re-occurrence in commercial poultry outbreaks with highly pathogenic virus, either H5N1 or H5N2 subtype, since there is a high degree of birds smuggled from countries with problems with these subtypes; introduced exotic birds, fighting or frozen meat, which sometimes contain the organs (Trachea, lung, intestines etc).

SOUTH AFRICA
In March of 2011, the HPAI affected to Ostriches, just 100 animals were deaths, the last presence of the virus in that country was in 2006 (2).

MEXICO
In October 1993, respiratory signs and decreased egg production in commercial layer hens in Mexico were associated withserological evidence for H5 AI. The virus was first isolated in May 1994 in broilers, and it did not cause any sign of disease, when experimentally inoculated into specific pathogen free (SPF) chicken. In addition, the virus possessed an amino acid sequence at the cleavage site of the HA, HA1/ HA2, that was compatible with a nonpathogenic strain (Pro-Gln-Arg-Glu-Thr-Arg/Gly). By the time the non-pathogenic H5N2 subtype was isolated in Mexico, the virus had already spread widely, and the option of eradication of the virulent strain from the Mexican chicken population had already surpassed resources of the industry (6, 23).
 
In January 1995 a highly pathogenic H5N2 influenza virus was detected in commercial broiler breeders 135 miles northwest of Mexico City in Queretaro México. In SPF chickens, the highly pathogenic strain A/Chicken/Queretaro/19/95 (H5N2) killed all the inoculated birds, with classical sign of fowl plague (13, 38).

Because of the eradication of H5N2 from Mexican chicken industry in 1994 -95 by depopulation methods was not economically possible. México was the first country to adopt vaccination as a method to reduce its spread, with the aim of eventual eradication. The feasibility of using vaccine to achieve these goals constitutes a major natural experiment and depends on the availability of high-quality vaccines (1,36).

In Mexico, an AI vaccination program was established in 1994. Initially, the program was instituted to control the HPAI H5N2 virus outbreak that occurred during that year (39). A commercial vaccine against AI was produced using the officially authorized virus strain A/Ck/México/CPA- 232/1994(H5N2). In this year, the HPAI virus was eradicated from all the chicken industry in Mexico and it was decided to continue the vaccination program to protect commercial flocks from LPAI H5N2 viruses. After almost two decades of using the AI vaccine in Mexico, commercial farms remain HPAI-free. More than 3 billion doses of inactivated vaccine and more than 2 billion recombinant vaccines, either fowl pox or NDV as vectors, have been used in the commercial flocks. In spite of this massive vaccination, respiratory signs in vaccinated flocks have been observed, due to a field challenged with the LPAIV.

The current increase in incidence of AIV infection is most likely related to antigenic drifts occurred in field AIV (19). Furthermore, private animal health laboratories have reported significant differences in cross hemagglutination inhibition (HI) tests between current fields isolates of LPAI H5N2 and the vaccine seed virus. These discrepancies observed during AI surveillance could be attributed to a gradual accumulation of antigenic drift. In fact, it was shown that LPAI H5N2 viruses in Mexico are constantly undergoing genetic drift, and that recent AI virus isolates have significant antigen divergence when compared to the AI vaccine strain (20). 

In Mexico, as in many other countries, AI surveillance is primarily carried out by the HI test using reference antigens or antiserum. This method is recommended by the World Organization for Animal Health (OIE) as a standard test to detect antigenic differences between circulating field virus and vaccine strain, as well as to evaluate vaccine efficacy. Antigens to set up official HI test or antigen to produce commercial inactivated vaccine are maintained and distributed by government official reference laboratory; these antigens are produced with AI viruses isolated more than a decade ago.

Although the Mexican government has recognized changes in the sequencing of the HA protein of avian influenza virusesthat are currently circulating in a chicken Mexican flocks, and the strain of the vaccine, at the moment the government has not provided a current strain of AIV to produce commercial vaccine, but inexplicably, they have provided to unofficial laboratories, an avian influenza virus strain H5N2 of the year 2006, to set up the official HI test.

The change of the influenza virus (antigen) that were used in the official HI test, was necessary because many chickens flocks that were affected with current field virus of low pathogenicity, was negative to the HI test, which used as antigen H5N2 avian influenza virus of 1994.

And it is documented that the percent homology of the HA gene sequence between field isolates and the vaccine strain is essential to decrease spread levels of field AIV strains (29, 37). The genomic variation found, might explain the permanence of LP AIV in Mexico since 1994, despite the use of both vaccination and stringent biosecurity measures.

In spite of the fact that millions of chickens have been vaccinated with AIV the low pathogenic, AIV is moving in Mexican chicken farms, affecting the productive parameters. In broilers, the mortality has increased two or three folds, basically due to respiratory problems, because the virus induces an obstruction in bronchia, causing asphyxia in chickens. The condemnations increasing, due to, that the virus is associated with bacteria opportunist like E. coli, its cause colisepticaemia. In breeders or layers the virus combine together with other respiratory viruses like NDV to decrease the production.

In many parts of the world AIV keeps circulating in the fowls, there are many reasons; one of them is the high level of maternal antibodies that have the chicken at the moment to get the AIV vaccine, in this scenario, the antibodies interfere with the performance of the vaccine, leaving the chicken with not protection against the pathogen AIV. We think that this situation provoke that some vaccine fail in the field. Garcia et al, have mentioned, that the maternal antibodies dramatically affected the immune response in chickens vaccinated at eight days of age (5).

Dr. Webster, found the same result when he worked, with vaccines and virus from Egypt (15). 

Mexico has the most extensive animal health campaign than any other country in the world with the H5N2 subtype of avian influenza virus. The Government has made changes and / or adjustments to the original health campaign, these changes came the year 2011. The country is divided into compartments, depending on their health status. Existing restrictions on movement of animals and their products or sub-products.

Another change that was made, was to omit the HI tests and viral isolation from private laboratories that were certified as official by the government, these results served to confirm disease-free flocks, now, all samples to verify free flock IA, take place in a government laboratory.

Another important change is the authorization to use autogenous avian influenza strains, to produce vaccine, as well as, they meet all the quality parameters established by the federal government and that these do not cause problems to the poultry industry.

In addition to allowing vaccine to enter the country from abroad, provided they are H5N2 and meet the same requirements as the vaccines made in Mexico. In the previous official animal health norm, all isolates of the H5N2 avian influenza virus, either low or high pathogenicity were reportable. Now only highly pathogenic is notifiable.

CONCLUSIONS

1. Avian influenza viruses have been and remain important public and animal health due to economic and human fatalities that cause 

2. AI virus by its genetic nature has the ability to mutate very quickly, emerging viruses that are mostly new to the immunological memory of human or animal population. This feature of the virus also generated highly pathogenic virus, which originally was one of low pathogenicity.

3. AI is a very dangerous virus and is capable of changing their life cycles (Either by glycosylation, , insertion or substitution events, some amino acids in different proteins in their genomes etc) when it feel that are trapped or destroyed by the immune system , the above in order to survive

4. Migratory birds are still an enigma in the spread and occurrence of the disease in affected countries.

5. The presence of the disease in poultry populations is determined primarily by discrete biosecurity measures and management of products and subproducts, as poultry flocks are free of the disease found in areas where the virus is enzootic.

6. The AI virus subtype H5 or H7 in humans has killed at an early age to adulthood.

7. It is known that H5N1 has the capacity to be transmitted occasionally from human to human. Such transmission, however, has only occurred in exceptional instances, usually involving very close contact with a patient during the acute phase of illness. To date, H5N1 has not spread beyond one generation of close contacts

8. The risk of transmission and adaptation of AI viruses from animals to humans and the increase in mortality is low (Asian H5N1, H1N1 North America), this is related to the cell receptors that have each species in their epithelial cells of the virus target organs.

9. Vaccination has helped to mitigate the disease in the flock population and reduce the number of. deaths in humans

10. There are areas in developing countries, which lack electricity, which affected the power and effectiveness of AI vaccines, the above difficult to control the disease in poultry populations in those areas

11. Different degrees of protection and immune responses have been obtained in some avian species (chickens vs waterfowl as, gulls or ducks ) that have been vaccinated with inactivated AI emulsified vaccine.

12. Maternal antibodies influence the good response from the vaccine. in some cases completely block the response, leaving the poultry population susceptible to disease.

13. The smuggling of live or dead animals as well as products and subproducts of poultry, may be the most important source of spread of a disease free country, more than the presence of  migratory birds.

14. Live bird markets, it seems an ideal environment for the transmission and survival of the virus and the crossing of these.

15. When statutory notifiable avian disease is confirmed action to confine and stamp out disease includes movement controls on susceptible species in the area around the premises, enhanced biosecurity, culling of susceptible poultry on the premises, and cleansing and disinfection of the premises.

16. The elimination of highly pathogenic virus either H5 or H7 subtype in poultry flocks, there seem not to be complicated, as long as they comply with the slaughter of affected and exposed birds, as well as controlling movement of poultry products and sub- products As well as epidemiological surveillance and biosecurity. Eg Many (USA Canada, Chile, etc) -

17. The measures taken between developing and underdeveloped countries to free poultry flocks the disease is dramatically different and are based primarily on financial support (compensation), the first countries, affected birds slaughtered, the suspect and the adjacent, coupled with strict biosecurity measures and movement of poultry products and sub-products, the latter have to comply with health campaigns, immunization and different levels of biosecurity measures.

18. Timely Notification of AI virus and transparency of governments and people involved in the context poultry - animal, help to control and possible eradication of the disease.

19. AIV emerge and re-emerge (not sure when) Ej, Holland with the subtype. H7N1in 2010 - re emerge in March. 2011. 

20. The press and other media (TV, radio, internet, etc) and some professors have been responsible for magnifying and sometimes exaggerate, the pathogenicity of the virus, this has affected the productive sectors (animals) and the economy of a country, as was the case in Mexico in 2009, with the swine flu H1N1 virus, which is then considered a pandemic and the year after they took off that title, but the damage tothe economy was already done. It is known that there were pressures to classify this virus as pandemic.

21. It is not easy a presentation of pandemic or epizootic with any subtype of the influenza virus, and that protection involved not only humoral immunity but also cellular and innate, there is also crossprotection between H9N2 vs. H5N1 subtypes, to name some, as there are some peptides homology along the HA protein of both subtypes.

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