Avian influenza: causes and pathogenesis

Causes of Avian Influenza

The cause of avian influenza in humans is the influenza A virus of the genus Influenzavirus of the family Orthomyxoviridae. It is referred to as shell viruses. The virion is irregular or oval in shape, covered with a lipid membrane, permeated with glycoprotein spines (spicules). They determine the haemagglutinating (H) or neuraminondase (N) activity of the virus and act as its main antigens. There are 15 (according to some sources, 16) variants of hemagglutinin and 9 - neuraminidase. Their combination determines the presence of subtypes of the virus, and theoretically 256 combinations are possible. The modern "human" influenza virus has combinations of antigens H1, H2, H3 and N1, N2, according to seroarcheological studies, a severe pandemic of 1889-1890. Was caused by a subtype of H2N2, a moderate epidemic of 1900-1903. - a subtype of H3N2, a pandemic of the "Spaniard" of 1918-1919. - H1N1, containing an additional protein obtained from the avian influenza virus. Epizootic influenza birds in recent years are associated with subtypes of H5N1. H5N2, H5N8, H5N9, H7N1, H7N3, H7N4. H7N7. In populations of wild birds, the subtypes H1, H2, N3, N2, N4 circulate; similar to the human influenza A virus.

Under the lipid membrane is a layer of the matrix protein of the M protein. Nucleocapsid, located under a two-layered shell, is organized as a spiral symmetry. The genome is represented by single-stranded RNA. Consisting of eight separate segments. One of the segments encodes the non-structural proteins NS1 and NS2, the rest encodes the virion proteins. The main ones are NP, which performs regulatory functions, M-protein, which plays an important role in the morphogenesis of the virus and protects its genome, and internal proteins - P1-transcriptase, P2-endonuclease and B3-replicase. Differences in the structural proteins of the avian influenza virus and human influenza represent an insurmountable species barrier that prevents the replication of the avian influenza virus in the human body.

Different subtypes of this virus have unequal virulence. The most virulent subtype of H5N1, which in recent years has acquired a number of unusual properties:

• high pathogenicity for humans;
• the ability to directly infect people;
• the ability to cause hyperproduction of pro-inflammatory cytokines, accompanied by the development of acute respiratory distress syndrome;
• the ability to cause multiorgan disorders, including damage to the brain, liver, kidneys and other organs;
• resistance to antiviral rimantadine;
• resistance to interferon.

The bird flu virus, in contrast to that of the human virus, is more stable in the environment. At a temperature of 36 ° C, it dies in three hours, 60 ° C - in 30 minutes, with the heat treatment of food (boiling, frying) - instantly. Well tolerates freezing. In the bird litter survives up to three months, in the water at a temperature of 22 ° C - four days, and at 0 ° C - more than a month. In the carcasses of birds remains active for up to a year. It is inactivated by usual disinfectants.

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Pathogenesis of avian influenza

At present, the mechanism of development of influenza caused by the H5N1 virus in humans has not been adequately studied. It is established that the place of its replication is not only epithelial cells of the respiratory tract, but also enterocytes. Taking into account general biological and immunopathological processes, it can be assumed that the pathogenesis of influenza A (H5N1) in humans will develop according to the same mechanisms.

Various hemagglutinins of avian influenza viruses have the ability to recognize and bind to the receptor - sialic acid, bound in the oligosaccharide of cell membranes with galactose. Hemagglutinins of human influenza viruses interact with the remains of this acid combined with a 2.6 bond to galactose, and the hemagglutinin of avian influenza viruses recognizes it in 2.3 bonds with galactose residues. The type of linkage of terminal sialic acid and conformational mobility of oligosaccharides of surface lectins are the main elements of the interspecies barrier for avian and human influenza viruses. Lectins of human tracheal epithelial cells include lectins with a bond type of 2.6 and do not contain oligosaccharides with a bond type of 2.3, characteristic of epithelial cells of the intestinal tract and airways of birds. Changes in the biological properties of the highly pathogenic strain A (H5N1), the appearance of the ability to overcome the interspecies barrier, can lead to the defeat of various types of cells in humans with the development of more severe forms of the disease. In the clinical picture of such pathologies, along with catarrhal syndrome, gastrointestinal lesions develop.

Epidemiology of avian influenza

The main reservoir of the virus in nature is migratory waterfowl belonging to the groups Anseriformes (wild ducks and geese) and Charadriiformes (herons, plovers and terns). The most important are wild ducks. Influenza viruses in Eurasia and America evolve independently, so migration between continents does not play a role in the spread of the virus, long-distance flights are critical. For Central Asia, the Central Asian-Indian and East Asian-Australian migration routes are important. They include routes going to Siberia via Malaysia, Hong Kong and China, i. E. Regions where there is an intensive formation of new variants of the virus. Less important are the East African-European and West-Pacific roads.

In wild waterfowl, the virus does not cause a clinically significant disease, although a large-scale heavy epizootic of influenza in polar terns is described. Viral replication of the virus occurs predominantly in the intestine and, accordingly, it is released into the environment with feces, to a lesser extent with saliva and respiratory material. In 1 g of feces contains the amount of virus sufficient to infect 1 million of poultry head.

The main mechanism of virus transmission in birds is fecal-oral. Waterfowl (ducks) are able to transmit the virus transovarially and, thus, serve as its natural natural reservoir and spread along the paths of their migration. They are the main source of infection for poultry, which, on the contrary, are ill with severe forms of influenza. Accompanied by mass deaths (up to 90%). The most dangerous subtype is H5N1. Infection occurs in conditions of free content and the possibility of contact with their wild counterparts. This is especially true for the countries of South-East Asia (China, Hong Kong, Thailand, Vietnam and other countries). There, along with large poultry farms, there are many small peasant farms.

The bird flu virus can affect mammals: seals, whales, mink, horses and, most importantly, pigs. Cases of penetration of the virus into the latter were noted in 1970, 1976, 1996 and 2004. These animals can also be affected by the human influenza virus. At present, people's susceptibility to such viruses is low. All cases of infection are recorded in those who have been in contact with the sick bird for a long time. The experiment in the UK on the introduction of various subtypes of the virus into the body of volunteers gave a negative result.

In Thailand, where the population is 60 million people, during the epizootic. Which affected two million birds, reliably established 12 cases of disease in humans. By 2007, about 300 episodes of "bird flu" in humans have been recorded. Officially recorded two cases of infection from a sick person.

These data indicate that. That circulating strains of avian influenza virus do not pose a serious threat to humans. Thus, it can be concluded that the interspecific barrier is sufficiently strong.

However, there are facts that suggest that avian influenza is a global threat. First, the above information can be interpreted from other positions.

• Even single cases of infection of people from birds and from patients indicate that. That the insurmountability of the interspecies barrier is not absolute.
• The actual number of cases of infection from poultry, and possibly even from sick people, given the actual situation in regions where epidemics are rampant, can be many times greater. During the epizootic of the H7N7 flu in Holland, 77 people became ill, one died. People who come into contact with patients have high antibody titres, which also indicates the possibility of transmitting the virus from person to person, but with the loss of virulence.

Secondly, the mutagenic potential of the avian influenza virus, especially the H5N1 subtype, is very large.

Third, pigs are susceptible to avian and human influenza viruses, so it seems theoretically possible to encounter pathogens in the animal's body. Under these conditions, their hybridization and the emergence of virus-associates, possessing a high virulence characteristic of the avian influenza virus, and at the same time capable of being transmitted from person to person, can occur. In connection with the massive spread of avian influenza this probability has increased dramatically. There are also cases of infection of people with swine flu, but simultaneous penetration of two viruses into the human body is still less likely.

Fourthly, it was proved by genetic methods that the Spanish pandemic of 1918-1919. Had a "bird's" origin.

Fifth, in modern conditions, thanks to the processes of globalization, the presence of fast transport modes, the possibility of spreading the assossant virus increases dramatically. Thus, it is fair to conclude that the probability of a new variant of the influenza A virus and the occurrence of a severe pandemic is very high.

Methods of mathematical modeling show that in a city with a population of 7 million (Hong Kong), the number of people at the peak of the epidemic can reach 365,000 people daily (for comparison, in Moscow during the pandemic flu in 1957 this number did not exceed 110 thousand people a day ). According to WHO experts, perhaps the rapid culling of birds during the epizootic in Hong Kong in 1997 prevented a pandemic of influenza. US experts predict that in the event of a pandemic in America, it will be necessary to hospitalize from 314 to 734 thousand people, perish from 89 to 207 thousand.

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