Natural reservoir of influenza a. Scientists warn of a new threat to human health

One of the most widespread infectious diseases of the 20th and 21st centuries, affecting entire countries and continents, is the common flu. It got its name from the French grippe - to pick up, which indicates the incredibly high contagiousness of the disease. The virus is transmitted by airborne droplets, easily penetrates human mucous membranes and quickly spreads throughout the population. The virus spreads across the globe, causing pandemics - large-scale outbreaks of disease that sweep over a country or a number of countries.

Despite a lot of research conducted by brilliant doctors and scientists, the development of a vaccine and antiviral drugs, the influenza virus still harbors enormous destructive potential for the world's population. Cases of the disease are carefully recorded and recorded throughout the world, and the collected data is submitted to the World Health Organization. The problem is so significant and widespread that back in 1967, the Influenza Research Institute was created in our country, which is still active today.

Every year, from 3 to 5 million people worldwide fall ill with influenza, and up to 500 thousand of them die from the disease or its complications. The virus is most dangerous for people with chronic diseases of the respiratory and cardiovascular systems; the mortality rate among them is 100 times higher than the average. Each influenza epidemic damages not only the health of the population, but also the economy of countries as a whole, since the infection temporarily disrupts the ability of working people to work.

The history of mankind knows several impressive examples of influenza pandemics. Thus, during the First World War, the Spanish flu swept across the planet, infecting 29% of its population, which at that time amounted to 550 million people. According to estimates, the number of its victims ranged from 50 to 100 million people - this figure exceeds the death rate for the entire period of hostilities. Today, there is a real threat of another mutation of the virus with consequences in the form of a pandemic of similar severity.

Pathogen

The causative agent of influenza is one of the most studied viruses today, as it is closely monitored by scientists around the world. However, this has still not brought humanity any closer to controlling influenza infection, due to its incredible variability. The influenza virus belongs to the Orthmyxoviridae family and is divided into 3 types:

• type A – found in humans and animals, most often causing massive outbreaks of the disease;
• type B is human, accounting for less than 20% of cases of the disease;
• type C is human, found in no more than 5% of cases.

Scheme of the structure of the influenza virus

The types differ in the type of outer membrane proteins - hemagglutinin (H) and neuraminidase (N). For example, the most common type A virus carries hemagglutinin type 1 and neuraminidase type 1, which is briefly referred to as H1N1. To date, viruses with antigens H1, H2, H3 and N1, N2 have been isolated from humans; other types of antigens are found in influenza pathogens in animals and birds.

The influenza virus has a fairly simple structure: it has a protein capsule surrounding an RNA molecule - its hereditary information. It encodes only 11 protein molecules, from which the entire virion is assembled. The pathogen was isolated from the material of a sick person back in 1931, and after the development of electron microscopy, it became possible to visually study its structure. The virion has a spherical shape and size up to 120 nm, its surface is dotted with “spikes” - neuraminidase molecules.

The pathogenicity of the influenza virus is ensured by its structural proteins:

• Hemagglutinin (HA) – serves to attach virions to body cells and is the main target for immune antibodies;
• Nucleoprotein (NP) – transports viral RNA from the nucleus to the cytoplasm during the assembly of viral particles;
• Neuraminidase (NA) is responsible for the release of new virions from the cell and prevents them from sticking together, which ensures high efficiency of infection of new targets;
• Internal membrane protein (M2) – forms a channel in the thickness of the cell membrane for virus penetration;
• Non-structural protein NS1 - suppresses the synthetic activity of the host cell, triggers the mechanism of its self-destruction (apoptosis).

Carriers of the influenza A virus are wild and domestic waterfowl: ducks, geese, plovers. Its final owners are humans, horses, and pigs. The hosts and sources of the remaining types (B, C) are only humans.

Alternate circulation of the virus in the body of humans and animals every few decades leads to significant changes in its genome. As a result, one or both surface antigens are replaced by others, as was the case with the bird flu pathogen in China in 2013. It acquired the H7N9 structure while retaining the ability to infect people.

Birds are a natural reservoir of infection in which all existing genetic modifications of the virus are preserved. Consequently, the Spanish flu genes responsible for the high contagiousness and lethality of the infection still circulate in nature, creating the danger of a repeat pandemic. WHO is closely monitoring the readiness of the virus for new devastating marches across the planet, assessing the current situation as halfway towards the virus acquiring highly pathogenic properties.

Mechanism of disease development

Flu outbreaks are strictly seasonal and occur during the cold season. As a rule, they begin after a slight thaw, which is preceded by frost. The air becomes humid and cool, which is an ideal environment for the virus to persist in the external environment for a long time. Short daylight hours and low solar activity also promote the survival of viral particles. The pathogen quickly accumulates in crowded places: in public transport, classrooms, work offices.

A sick person releases the influenza virus with saliva released from the nose when coughing, sneezing, or talking. The most dangerous droplets of mucus formed when sneezing are extremely small in size, spread over long distances and easily penetrate the respiratory tract of other people. Once on the mucous membrane of the nose and pharynx, the virus attaches to its cells - epithelial cells - and penetrates inside.

In the cell, it sheds its protein coat and starts the mode of reading its genetic information, transferring it to the protein synthesis station - ribosomes. The translation process is ensured by the viral enzyme reverse transcriptase, which builds a DNA chain complementary to influenza RNA and integrates it into the cell genome. The virus completely subordinates cellular metabolism to its needs and its components are spent on the assembly of viral particles. When enough of them accumulate in the cytoplasm, they come out, rupturing the cell and leading to its death. New viral particles infect neighboring cells and the cycle of their reproduction repeats.

Dead epithelial cells slough off from the surface of the mucous membrane, exposing the submucosal plate. In response to the changes occurring, immune defense mechanisms are launched with the development of an inflammatory reaction. Immune cells strive to localize the site of viral damage by consuming infected epithelial cells and their remains. The circulatory system also reacts: blood rushes to the site of inflammation, its liquid part enters the tissue and edema forms as a barrier.

Bare areas of the mucous membrane lose their barrier function and allow viral particles to pass into the underlying tissue. Thus, they enter the bloodstream, spread throughout the body and, together with the products of cellular decay, cause fever, local and general toxic reactions. The virus has a damaging effect on the vascular wall, it becomes brittle, and its permeability to the liquid part of the blood and formed elements increases. It suppresses the activity of the immune system, preventing the synthesis of antiviral and other classes of antibodies. The protection of mucous membranes in all organ systems is significantly affected, which facilitates the penetration and proliferation of various pathogenic bacteria.

In response to the presence of viral particles in the tissues of the body, cells of the immune system produce specific antibodies that bind and destroy the pathogen. At the site of the entry gate of the virus - the mucous membrane of the upper respiratory tract - immunoglobulins of classes A, M, G are synthesized, which prevent its re-entry. They remain highly active for 3-5 months after infection.

Class M immunoglobulins to hemagglutinin and neuraminidase are produced in sufficient quantities on the 10-14th day of the disease, reaching their peak after 2 weeks. Their presence in the blood indicates an acute infection and is widely used in diagnosis. Immunoglobulins of class G accumulate in sufficient quantities somewhat later - 1-1.5 months from the onset of the disease. They last for life and protect a person from re-infection with the same type of virus. In turn, other antigenic variants of the pathogen can cause a repeat case of influenza in the next epidemic season.

The influenza virus is completely eliminated from the body on average 10-14 days from the onset of the disease However, complications may arise at a later date. Those of them that are directly related to the circulation of virions in the blood are called early. Among them are brain, massive bleeding. Late complications occur after the virus has completely disappeared from the blood and are associated with profound disorders of the immune system and microcirculation. The most severe and dangerous among them is considered bacterial, which is extremely difficult to treat, especially in older people.

Classification

Formally, influenza can be classified as a broad group, since it fully fits its criteria. The disease is viral in nature and occurs in an acute form; the target for the action of the pathogen is the mucous membrane of the respiratory tract. However, the characteristic clinical picture, morbidity in the form of epidemics and pandemics, as well as the uncontrollability of the virus despite the arsenal of therapeutic and prophylactic agents, forces each case of influenza to be separately registered.

Influenza is classified according to severity:

According to the nature of the flu, there are:

1. Uncomplicated.
2. Complicated:
   • early complications - associated with the direct impact of the virus on the body;
   • late complications - associated with changes that the influenza virus leaves behind. They can manifest themselves in the form of a bacterial infection and exacerbation of chronic diseases.

Clinic

Influenza occurs cyclically with the passage of certain stages of development. Immediately after infection, the virus begins to multiply in epithelial cells without showing itself in any way - this is how the incubation period of the disease passes. It lasts for influenza type A up to 2 days, for influenza type B up to 3-4 days. As soon as the pathogen accumulates in sufficient quantities to penetrate the blood, the next period begins - the height of the disease.

The active phase of the disease begins acutely with severe chills, weakness and an increase in temperature to 38-40 degrees C. Fever reaches its maximum on the second day of illness and then gradually decreases. It is associated with a massive release of viral particles into the blood and rarely persists for more than 5 days. Fever in later periods of the disease is usually associated with the addition of a bacterial infection.

People sick with influenza have the characteristic appearance of a “tear-stained child”: the face becomes puffy, the skin and conjunctiva are hyperemic, and the eyes are shiny. Often, due to pain in the eyes, patients experience increased lacrimation and photophobia. The patient's mouth is slightly open, as nasal breathing is difficult.

In general, the symptoms of influenza fit into 2 broad syndromes: intoxication and catarrhal.

Manifestations of influenza

Intoxication manifests itself:

• Severe headache, which is usually localized in the frontal part and has a bursting character;
• Soreness in muscles, joints, muscle weakness;
• Weakness, weakness, malaise;
• A feeling of palpitations, a rise in blood pressure at the onset of the disease and its persistent decrease below normal in the early period of recovery;
• Bleeding from the mucous membranes, small rashes on the skin, increased thrombus formation.

Catarrhal syndrome is a consequence of inflammation and swelling of the mucous membrane of the respiratory tract. It manifests itself:

• A dry, irritating cough at the beginning of the disease and a cough with a small amount of mucous sputum closer to recovery;
• with minor discharge;
• Hoarseness of voice.

This is how uncomplicated influenza of mild or moderate severity occurs. The symptoms gradually weaken and after 7-10 days the person recovers. However, the specific effect of the virus on the body leads to the fact that a person suffers from tension headaches, weakness, and increased fatigue for several months after the illness.

The hypertoxic form of influenza, which is typical for older people, is much more severe. and patients with severe immunodeficiency. It is manifested by symptoms of damage to the central nervous system and multiple organ failure:

1. Convulsions;
2. Rave;
3. Fountain vomiting;
4. Visual hallucinations;
5. Confusion or complete loss of consciousness;
6. A sharp drop in blood pressure;
7. Excitement and psychosis;
8. Severe shortness of breath;
9. Bleeding;
10. Wearisome cough;
11. Chest pain.

Complications of influenza develop in 10-15% of patients and are most often represented by pneumonia, since the virus is able to multiply directly in the cells of the bronchial tree and alveoli. Viral pneumonia is characterized by a severe course, severe respiratory failure and resistance to antibacterial therapy. The patient is bothered by a severe cough with copious mucous sputum, which is often streaked with blood. His skin becomes pale with a uniform bluish tint, his hands and feet are cold to the touch. Severe shortness of breath occurs with little physical exertion and at rest, which is aggravated by the addition of pulmonary edema.

Flu in pregnant women

Pregnant women, due to their condition, are one of the most vulnerable categories to the influenza virus. In the body of the expectant mother, under the influence of hormones, the activity of the immune system decreases, which is necessary for the normal bearing of the child. In this regard, pregnant women easily become infected with influenza and are more likely than others to suffer from its complications. It is noticed that The severity of the disease increases starting from the 3rd trimester - the mortality rate during this period is about 17%. The risk of complications and adverse outcomes from influenza increases significantly if a pregnant woman has chronic somatic diseases.

The general clinical picture differs little from that described above: body temperature rises, a dry cough, pain in the front of the head, muscles, and joints appear. Shortness of breath increases, feet, legs, and hands swell.

Signs of developing complications include:

• Increased respiratory rate over 30 per minute;
• Impaired consciousness;
• Tachycardia;
• Chest pain.

Viral pneumonia during pregnancy develops extremely quickly: it takes only a few hours for the pathogen to cause extensive lung damage. Complications, in turn, increase the risk of premature birth and fetal death. This is due to damage to the blood vessels of the placenta and disruption of fetal-placental blood flow. Caesarean section or childbirth during the height of the disease often ends in the death of the mother due to massive obstetric hemorrhage, severe respiratory failure, and postpartum purulent complications.

Atypical influenza

Changes in the protein structure of the virus invariably entail the emergence of new ways of interacting with the host body, and therefore the symptoms of the disease change. Thus, avian influenza H5N1 is characterized by a longer incubation period - it lasts from 1 to 7 days, after which a typical infection pattern develops. However, it is more capable of multiplying in the lower parts of the respiratory tract - bronchioles and alveoli, causing a debilitating cough with bloody sputum. The severe course of the disease is accompanied by respiratory distress syndrome - a severe disturbance of gas exchange in the lungs with the need for artificial ventilation.

Swine flu H2N3 is characterized by the addition of symptoms of damage to the gastrointestinal tract: vomiting, abdominal pain, loose stools. Otherwise, it proceeds similarly to the typical form of influenza, starting with fever, cough, and severe general weakness.

Diagnostics

Diagnosis of influenza is carried out by a general practitioner in the case of an outpatient appointment and by an infectious disease specialist after a patient is referred to him or admitted to a hospital. The diagnosis is established during the collection of anamnesis, examination of complaints, examination of the patient and is confirmed by laboratory tests. Influenza is favored by the acute onset of the disease in the cold season after contact with a sick person or visiting crowded places. A characteristic combination of symptoms for influenza is a high temperature from the first day of illness with severe intoxication and a dry cough.

During the examination, first of all, the doctor pays attention to the patient’s appearance:

1. Skin color – pale or excessively ruddy due to fever and intoxication, bluish due to respiratory failure;
2. The presence of a petechial rash on the skin and mucous membranes is a pinpoint rash that appears due to increased permeability and fragility of capillaries.

Examination of the pharynx reveals hyperemia of the posterior wall of the pharynx and its granularity. The palatine tonsils do not protrude beyond the edge of the arches or are slightly hypertrophied. Their mucous membrane is smooth, shiny, there are no plaques on it (unless bacterial flora is attached).

Enlargement of peripheral lymph nodes with influenza is rare; as a rule, the submandibular, cervical and intrathoracic ones react. Upon auscultation, the doctor notes an increase in heart rate, muffled heart sounds, no wheezing or it is dry. If the flu is complicated by pneumonia, edema or pulmonary infarction, then moist rales and silent zones appear in which breathing cannot be heard. The pulse is fast, weak and tense.

When the central nervous system is damaged, signs of irritation of the meninges appear. These include tension in the neck muscles, the inability to fully straighten a leg bent at the hip joint in a supine position (Kernig's symptom). Inflammation of brain tissue - encephalitis and cerebral edema occurs with impaired consciousness, loss of sensitivity and impaired motor activity.

The doctor finally confirms the diagnosis of influenza by prescribing a series of laboratory tests:

All people over 35 years of age admitted to hospital for influenza undergo an ECG to identify possible abnormalities in the functioning of the heart. If pneumonia is suspected, an X-ray of the lungs is performed, and it is especially important to conduct the study on time in pregnant women. The pregnant uterus is protected from radiation with a lead apron. Patients with moderate to severe forms of the disease undergo spirometry, a method for assessing the function of the respiratory system. With pulmonary edema and pneumonia, the vital capacity of the lungs decreases, but the peak expiratory flow remains normal.

Treatment

Influenza is treated by an infectious disease doctor together with a pediatrician (for children), an obstetrician-gynecologist (for pregnant women) and other specialized specialists (for people with chronic diseases). Mild forms can be treated on an outpatient basis, with the issuance of a certificate of incapacity for work for the period of contagiousness of the patient. Patients with moderate, severe, complicated influenza, pregnant women and children are hospitalized in an infectious diseases hospital.

During the height of the disease, bed rest with an easily digestible diet is recommended. You should drink at least 2 liters of warm liquid with a high content of vitamin C per day: currant, cranberry, lingonberry juice, compote, tea with lemon. Comprehensive drug treatment is carried out, which is aimed at preventing further replication of the virus, eliminating intoxication and preventing bacterial complications.

Antiviral drugs for influenza with proven clinical activity include:

Among other groups of drugs for the treatment of influenza, the following are prescribed:

• Inducers of interferonogenesis– tablets enhance the production of antiviral antibodies by immune cells (kagocel, ingavirin);
• Interferon preparations– increase the concentration of protective antibodies in the blood of patients (cycloferon);
• Antipyretics– alleviate the patient’s condition when fever is poorly tolerated (paracetamol, ibuprofen);
• Anticongestants– medications that relieve nasal congestion (xylometazoline);
• Vitamin C– to protect the vascular wall from the toxic effects of the virus;
• Expectorants– thin sputum, facilitate its removal (ambroxol, acetylcysteine);
• Antibiotics– reduce the risk of bacterial complications (ceftriaxone, azithromycin, amoxiclav, metronidazole);
• Saline solutions, 5% glucose solution– administered intravenously to eliminate intoxication;
• Hemostatics– to stop bleeding (etamsylate, aminocaproic acid).

Patients with severe respiratory failure are given respiratory support - oxygen-enriched air is supplied through an intranasal tube.

Folk remedies can only be used as an addition to the main therapy in order to increase the body's resistance to bacterial infections. Antiviral properties are attributed to phytoncides of onion and garlic, but they are effective only at the stage of disease prevention. Inhaling their fumes before visiting crowded places reduces the risk of infection, but does not completely eliminate it. It is advisable to take folk remedies with a high content of vitamin C orally: a decoction of rose hips, rowan, and black currant leaves. To restore the body's defenses, you can use echinacea extract, ginseng root, honey, and propolis.

Prevention

Flu prevention is carried out:

1. Specific methods - vaccination;
2. Nonspecific – quarantine measures, strengthening the body’s nonspecific defenses.

Vaccine

In many countries around the world, flu vaccination is included in the national vaccination calendar and is a mandatory procedure. In the Russian Federation, pregnant women, children, people with chronic diseases and the elderly are eligible for free vaccination. They should contact a general practitioner at their place of residence 1-1.5 months before the start of the predicted influenza epidemic, receive a referral for vaccination and get vaccinated in the vaccination office. All other categories of citizens are immunized on a paid basis: the vaccine itself is purchased at the pharmacy chain at your own expense.

The main condition for successful immunization is that at the time of vaccine administration the person must be healthy or in remission of a chronic disease.

The flu vaccine is produced annually based on the expected strain of the virus. The pathogen circulates between the southern and northern hemispheres of the earth, making it possible to guess which strain will cause an epidemic in the coming season. The flu shot can be:

State medical institutions are supplied with a domestic inactivated vaccine containing antigens of influenza viruses type A and B. Vaccination of pregnant women is safest in the 2nd and 3rd trimesters; it is recommended to start it from the 14th week of pregnancy during the epidemic season. The issue of immunization is decided in each case individually by an obstetrician-gynecologist, taking into account the risk of infection.

Vaccination significantly reduces the risk of severe influenza and its complications, however, it must be carried out in a timely manner - at least 2-3 weeks before the outbreak of the epidemic.

Non-specific methods

These include:

1. Removal of patients from visiting children's institutions, work groups, and public events for a period of 3 to 7 days - the time of clinical manifestations of the disease;
2. Frequent ventilation of premises and daily wet cleaning;
3. Wearing a gauze or disposable mask in public places; it should be changed at least once every 2 hours;
4. Treatment of the nasal passages in the midst of an epidemic - it prevents contact of the virus with epithelial cells;
5. Taking multivitamins and echinacea tinctures during the cold season.

Many people suffer from a so-called “cold” on their feet, while continuing to lead an active lifestyle, which only contributes to the spread of the epidemic. It is extremely difficult to assess the existing symptoms without consulting a specialist, therefore the necessary treatment is delayed and the risk of complications increases. Timely prescribed antiviral drugs reduce the likelihood of a negative outcome from the flu to a minimum, due to which the period of disability is shortened to 5-7 days. In healthy adults, the main danger of the disease is the addition of bacterial complications against the background of a pronounced decrease in immunity. Self-treatment of the flu at home is unacceptable, so if characteristic symptoms appear, consult a doctor as soon as possible.

Video: flu, Dr. Komarovsky

Avian influenza is a highly contagious viral infection that can affect all species of birds. The most sensitive domestic species are turkeys and chickens. Wild bird species can serve as vectors of infection. Due to natural resistance, they themselves, as a rule, do not get sick and can cover considerable distances during the migration process. The natural reservoir for avian influenza viruses (AIVs) are waterfowl, which are most often responsible for introducing infection into households.

Avian influenza viruses belong to the influenza A viruses of the ORTHOMYXOVIRIDAE family. There are several subtypes of the pathogen, which are determined depending on the characteristics of the antigenic structure of hemagglutinin (H) and neuraminidase (N). Currently, 15 H subtypes (H1 - H15) and 9 neuraminidase subtypes (N 1 - N 9) are known, which can reassort in various combinations. Among the most pathogenic for poultry are viruses with the antigenic formula H 7N 7 (chicken plague virus) and H 5N 1, which can cause the complete death of chickens.

Over the past 7 years, the avian influenza viruses H 5N 1 and H 7N 7, as a result of mutations, have sharply changed their biological properties and acquired the ability not only to overcome the host barrier with direct infection of humans (bypassing the intermediate host), but also to cause extremely severe clinical forms of the disease, significant some of which end in death.

Isolated viruses of the H 5N 1 subtype actively reassort and, overcoming the interspecies barrier, are “directed” from the reservoir of waterfowl to domestic birds, and, more recently, to wild birds living on land and to humans. This dictates the need for broader infection surveillance and control, especially since the influenza virus (unlike other respiratory agents) spreads unusually quickly and cannot be controlled by traditional isolation, quarantine, or travel advice. This makes it urgent to strengthen influenza surveillance to determine the factors that allow avian virus to be transmitted to humans and to subsequently develop effective vaccines against the H5 virus for both humans and animals.

Currently, the virus is more widespread in nature due to its adaptation to other mammals (cats, dogs, pigs).

Clinical picture of the disease in humans

The incubation period for influenza A (H 5N 1) is usually 2-3 days, varying from 1 to 7 days. The disease begins acutely with chills, myalgia, possible sore throat, and rhinorrhea. In Southeast Asian countries, more than half of the patients had watery diarrhea in the absence of mucus and blood in the feces, and repeated vomiting in a quarter of cases. An increase in body temperature is one of the early and persistent symptoms. Already in the first hours of illness, the temperature exceeds 38C and often reaches high and hyperpyretic values. At the height of the disease (on the 2-3rd day of illness), damage to the lower respiratory tract (lower respiratory syndrome) is characteristic with the possible development of primary viral pneumonia: cough, shortness of breath and dysphonia. The cough is usually wet, and there is often an admixture of blood in the sputum. Auscultation - hard breathing, wheezing. On a chest x-ray in the early stages, nonspecific changes in the lungs are found - diffuse, multifocal or individual infiltrates, which are capable of rapid spread and fusion. In some cases, segmental or lobar compactions may be detected. The progression of the disease is accompanied by the development of respiratory failure and acute respiratory distress syndrome.

Manifestations of pantropism of the virus and developing during the process of intoxication can be damage to the liver and kidneys; more than 30% of patients develop acute renal failure.

Young children experience severe disease. Encephalitis may be added to their main syndromes. In this case, the symptoms are supplemented by severe headache, vomiting, impaired consciousness and nausea.

The prognosis is usually unfavorable. Mortality reaches 50-80%. Death is usually observed in the second week of illness.

Chemoprophylaxis

Chemoprophylaxis of avian influenza is carried out by taking interferon inducers (cycloferon and amixin), Remantadine, Algirem, Arbidol and Oseltamivir (Tamiflu) as antiviral drugs. Chemoprophylaxis is most effective in risk groups, among contact persons and in foci of infection. The duration of administration is equivalent to the period of onset of the convalescence stage.

The use of symptomatic agents is indicated. For hyperthermia, antipyretic drugs (paracetamol, ibuprofen or Nise) are indicated.

Drugs that are not used in the treatment of influenza A (H 5N 1): salicylates (aspirin), analgin. Analgin and anti-grippins are strictly contraindicated for the treatment of bird flu.

Antibiotics are prescribed only if mixed pneumonia is suspected.

Conclusion

An alarming aspect is the possibility of simultaneous co-infection of people with human and avian viruses with the resulting emergence of reassortants carrying surface genes from avian viruses, and internal genes from epidemic human viruses, which can give the pathogen the ability to transmit in the human population and give rise to a new pandemic virus. In addition, there is concern about the possibility of direct transmission of the avian virus from person to person.

Research Institute of Influenza RAMS

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Transcript

1 UDC:636.5 NATURAL RESERVOIR OF INFLUENZA VIRUSES A O. N. Pugachev, M. V. Krylov, L. M. Belova (Zoological Institute of the Russian Academy of Sciences) Influenza viruses belong to the family. Оrthomixoviridae (Greek orthos - correct, true, tuha - mucus). This family includes five genera: influenza viruses A, B, C, Influenza viruses and Isaviruses. The supraspecific taxonomic category “genus” is often replaced by the term “phylum”. Influenza viruses of the genus A have been found in representatives of taxonomically different groups of birds and mammals. The taxonomy of influenza virus subgenera within genus A is based on the antigenic characteristics of two types of surface glycoproteins: hemagglutinin (H) and neuraminidase (N). Currently, there are 16 H subtypes and 9 N subtypes. The term “serovariant” or “serotype” is sometimes used. Theoretically, these subtypes of influenza A viruses can produce 144 pairs of combinations; only 86 have actually been registered, of which they were found in birds. Viruses of genus B infect only humans and have one type H and N. Viruses of genus C cause sporadic diseases in humans and pigs. The Togoto-like viruses genus includes the Togoto (prototype virus) and Dory viruses; which are transmitted by ticks, rarely infect humans. Representatives of the genus Isavirus cause infectious salmon anemia (ISA). These viruses in Norway were the cause of mass mortality of Atlantic salmon, salmon (Salmo salar). The ISA virus was isolated from coho salmon (Onchorhynchus kisutch) and mykiss (Parasalmo mykiss). Brown trout (Salmo trutta) and mykiss (Parasalmo mykiss) were experimentally infected with the ISA virus. Presumably, representatives of the genus Isavirus can infect mollusks, crustaceans and other marine invertebrates. Isaviruses are very close to influenza A viruses, so the possibility of recombination and reassortment of genes between these viruses with unpredictable consequences cannot be ruled out. This problem requires close attention and special research. Representatives of the family Orthomixoviridae are single-stranded RNA viruses that lack DNA copies in their replication cycle. -12-

2 International Bulletin of Veterinary Medicine, 2, 2008. Among RNA-containing viruses, families are distinguished with a positive genome (+), capable of being directly translated into protein (Coronaviridae) and with a negative genome (-), on which messenger RNA is first synthesized, which is then transformed on ribosomes into protein. The latter include representatives of the family. Orthomixoviridae. RNA replication in viruses of this family occurs in the nucleus, and self-assembly occurs in the cytoplasm on the plasma membrane with the inclusion of virus-specific proteins. RNA molecules are packed randomly into a helical nucleocapsid with a diameter of 9-15 nm. Orthomyxoviruses of genus A are characterized by a segmented genome consisting of eight fragments. Most of the genome fragments (I, III, IV, V, VI) correspond to the colinearity rule: one gene - one protein. Fragments (II, VII, VIII) encode two reading frames, the transcripts of which are subject to splicing. Thus, the genome of influenza A viruses encodes 11 proteins. The segmentation of the genome allows, during mixed infection with heterogeneous strains of the virus, the exchange of RNA molecules between them, as a result of which the emergence of new varieties of influenza is possible. Complete replacement of genome fragments usually occurs as a result of gene reassortment between viruses that are far apart phylogenetically. Influenza A viruses have been recorded in representatives of 18 orders of birds. In total, there are from 28 to 30 orders in the class of birds. It is safe to assume that all species of birds are susceptible to influenza A viruses and the final solution to this issue is only a matter of time. Traditionally, the main reservoirs of influenza viruses in nature are considered to be migratory birds leading an aquatic or semi-aquatic lifestyle. Such groups of birds primarily include representatives of the orders Anseriformes (mainly ducks, geese, swans) species and Charadriformes (mainly gulls, terns, waders) species. All currently known subtypes of avian influenza viruses were found in these ecological and taxonomic groups of birds. Meanwhile, in the class of birds there are about species. Most of these species (5700) are included in the order Passeriformes. Passeriformes surpass all known birds not only in species composition, but also, most importantly, in numbers. The average abundance in Europe of tree sparrows, warblers and house sparrows exceeds that of mallards by 6.9, 9.6 and 24.4 times, respectively. A qualitatively and quantitatively rich group of hosts, in this case passerines, theoretically represents the greatest opportunities for the reservation and spread of influenza viruses. Along with the greatest diversity and high numbers, passerines have a number of features that enhance their role in the circulation and reservation of the influenza virus. Passerines are characterized by a high reproduction rate and a rapid change of generations. A number of passerine bird species have two or even three broods during the summer season. When the house sparrow (P. domesticus) reproduces three times, there may be about chicks per pair. The increase in the number of house sparrows in certain parts of the range occurs not only due to reproduction, but also as a result of the migration of birds that nested to the north. Moreover, the abundance of house sparrows in the second half of July can exceed their density during the initial nesting period by almost ten times. Significant increase - -13-

3. An increase in the number of finch (Fringilla coelebs) was also noted in July. Many passerines are characterized by high population densities in most landscapes. Their density is particularly high in agricultural landscapes. A number of passerine species (sparrows, swallows, starlings, finches, corvids) are increasing their numbers in populated areas, thereby creating a direct threat of infection with the influenza virus in poultry. The high population density and the presence of a huge number of young individuals susceptible to influenza create favorable conditions for the circulation of influenza viruses among passerine birds. It was noted that the increase in the number and density of passerine bird populations due to reproduction and subsequent movements during June-July coincides with outbreaks of influenza during this period in poultry. Subtypes of influenza A viruses differ not only in antigenic characteristics, but also in the severity of the diseases they cause - in virulence. In English-language, and recently in Russian-language literature, the concept of “virulence” is replaced by the term “pathogenicity”. Pathogenicity (Greek pathos - suffering, disease, genes - giving birth, born) - pathogenicity, the ability to cause disease. Virulence (Latin virulentus - poisonous) - the degree of pathogenicity (pathogenicity), depends on the properties of the pathogen and the susceptibility of the infected organism. Virulence is judged by the severity of the disease caused and mortality among infected animals. There are 10 subtypes of influenza A virus recorded in the human population: H1N1, H2N2, H3N2, H3N8, H5N1, H7N2, H7N3, H7N7, H9N2, H10N7. Only three of them (H1N1, H2N2, H3N2) turned out to be the causative agents of influenza pandemics in the 20th century. There have been relatively rare cases of human infection with virus subtypes H5N1, H7N2, H7N3, H7N7, H9N2, H10N7 directly from birds, bypassing the so-called “intermediate hosts”. The most comprehensively tracked cases of human infection directly with the highly virulent subtype of the H5N1 avian influenza virus. According to WHO, 317 cases of human infection with the H5N1 avian influenza virus subtype have been reported in various countries, of which 191 were fatal. The ability of highly virulent subtypes of avian influenza virus to directly infect people creates conditions for their simultaneous coinfection with epidemic subtypes of human influenza virus with the subsequent emergence of reassortants carrying genes of both subtypes. As a result of this gene exchange, a new pandemic virus may arise. Nine subtypes of influenza A virus have been detected in passerine birds: H3N1, H3N2, H3N8, H5N1, H7, H7N1, H7N7, H9N2, H13 (Table 3). Of these, three subtypes H5N1, H7N7 and H9N2 have acquired the ability to infect people directly, bypassing “intermediate hosts”. Influenza virus subtypes H5N1, H7N1, H7N7 and H9N2 have caused devastating epidemics in poultry in many countries (Table 1). A study of the spread of influenza epizootics over the past 10 years has shown that the highly virulent subtype of the H5N1 influenza virus has a worldwide distribution. Of great concern is the report of a high percentage of infection with the H5N1 influenza subtype of tree sparrows, as well as the detection of antihemagglutinins to the H5 influenza subtype in young, sedentary and migratory passerines in the summer. All these facts convincingly indicate the circulation of influenza viruses in the breeding area. Residents, mainly passerines - -14-

4 International Veterinary Journal, 2, 2008. Epizootics of influenza A in poultry Table 1 Continent, country Date Virus subtype Australia, Pakistan 1994 H7N3 Mexico Mexico Asia, Africa, Europe, Middle 1997 H5N1 East, Hong Kong, Russia Australia H7N4 England, Ireland 1998 H7N7 H5N9 H7N2 Belgium 1999 H7N1 China H9N2 Canada 2000 H7N1 Germany, Pakistan 2001 H7N7 H7N H7N2, Chile H7N3 Belgium, Germany, Holland 2003 H7N7 Hong Kong H5N1, H9N2 Denmark H5N7, Canada H7N3 Republic of Korea H5N1 H7N2 Canada, Pakistan 2004 H7N3,H7N2 Taiwan, South Africa H5N11 Russia 2005 H5N1 . Southeast Asia H5N1 birds can be considered as a long-term reservoir of influenza virus in nature. Retrospective serological surveys of long-distance migrants (swallows, warblers, flycatchers, finches) showed that they become infected with influenza in the breeding area and then, during the autumn migration, spread the virus to wintering places - Africa to Guinea and Kenya, South Asia and India. The migration routes of anseriformes intersect with the migration routes of passerines and pass through the habitats of sedentary passerine species. Thus, the East Atlantic migration route partially overlaps the Black Sea-Mediterranean, East African - West Asian, Central Asian and East Asian - Australian migration routes of the population - -15-

5 Table 2 Survival of influenza A viruses in the external environment Substrate Temperature Survival Author(s) Water 70 C 2-5 min. -“- 60 C 10 min. -“- -“- 55 C 60 min. -“- -“- 22 From 4 days. Down, feathers, room from 18 to 120 days. bird houses Virus-containing 4 From 2-3 months. -“- suspension Water 0 C for more than 30 days. Chilled bird carcasses day. -“- frozen 447 days. -“- Virus-containing -20 C for several years -“- suspension Blood in ampoules -60 C for more than 6 years Exudate in ampoules -60 C -“- -“- tions of wild birds. Phylogenetic analysis of the nucleic acid sequences of influenza A viruses from various hosts showed that all animal influenza viruses are evolutionarily related only to birds, as a natural reservoir. It is clear that birds can be considered as the main reservoir of influenza A viruses in nature. However, when assessing the epidemiological situation, it is extremely necessary to take into account the role of mammals (primates, lagomorphs, rodents, carnivores, pinnipeds, cetaceans, equids and artiodactyls) in the circulation of influenza viruses and, above all, domestic animals: cats, dogs, rabbits, pigs, horses, cattle and, especially, synanthropic rodents. The ability of influenza viruses to survive for a long time in the external environment (Table 2) further complicates the problem. When solving practical problems, a systematic approach is needed to better understand some phenomena in the natural circulation of influenza viruses and, in particular, to explain the occurrence of influenza outbreaks in summer and winter. It is clear that in the fight against influenza, restrictive measures alone are insufficient; constant monitoring of influenza viruses and the creation of highly effective vaccines are necessary. We thank Dr. V. A. Paevsky for advice on bird taxonomy. Reservoir viruses influenza A in nature. O.N. Pugachev, M.V. Krylov, L.M. Belova SUMMARY Influenza A viruses have been isolated from many species from 18 orders of birds and 8 orders of mammalian including humans and domestic animals: pigs, horses, cattle, cats, dogs, rabbits and synanthropic rodents. The number of the species of Passeriformes (5700) and their quantity dominate in class Aves. Detection of antibody to influenza A in serum young resident and longistance migration Passeriformes birds indicated that. Passeriformes birds may play an important role in the natural reservoir and transmission of influenza virus. LITERATURE -16-

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Most of us perceive the flu as just one of the minor troubles. But this is a misconception: the flu should not be underestimated. The infection spreads so easily through airborne droplets that it affects a significant portion of the world's population every year. Influenza and other infectious diseases of the respiratory tract are the most common viral diseases in humans. They are the cause of death for many people. Due to mass morbidity, the economic damage from them is enormous in all countries.

The flu virus changes so quickly that no one is immune to all its varieties, and every year experts have to develop a new vaccine. Until now, we have been talking about the usual types of influenza, but starting in December 2003, an unprecedented outbreak of avian influenza occurred in the world, affecting 38 countries. The countries of Southeast Asia were primarily affected. Currently, an epidemic of avian influenza caused by the influenza A virus H5N1 has been reported in many countries in Europe, Asia and Africa. Human cases have been reported in 7 countries. 3 countries from this number border on Russia.

Despite emergency measures to prevent the spread of avian influenza, which resulted in the destruction of more than 100 million poultry populations, the H5N1 virus has established itself in wild bird populations and has acquired the ability to infect humans, suggesting that it is a possible precursor to the pandemic virus. As of March 21, 2006, 185 people fell ill in the world, of which 104 died.

It's not unusual for chickens to get the flu. There are many more varieties of bird flu than human flu. Avian influenza is a highly contagious viral infection that affects all species of birds. The most sensitive domestic species are chickens and turkeys. The natural reservoir for avian influenza viruses is waterfowl, which are most often responsible for introducing the infection into households.

There has always been flu among birds. In wild birds, the disease occurs in the form of enteritis (intestinal damage) without visible signs of general disease. This indicates a high degree of adaptation of influenza A viruses to wild birds, which are their natural hosts. The virus persists in water for a long time (6 - 8 months), and the water-fecal route of infection of birds is the main mechanism for maintaining the influenza virus in nature, from where it penetrates into populations of poultry and animals. The highly pathogenic virus can survive in the environment for long periods of time, especially at low temperatures. For example, it can survive in bird droppings for up to 35 days at 4 degrees C. At 37 degrees C, the virus remains viable in bird droppings for at least 6 days.

Avian influenza viruses can be transferred from farm to farm when moving live birds, as well as by people through shoes and clothing, contaminated by transport wheels, equipment, and feed. For these reasons, poultry workers are not advised to keep poultry. Such demands must be taken seriously. When a disease occurs, the most important and effective infection control measures are the rapid destruction of the entire population of sick birds or those in contact with them, the mandatory collection and burial or burning of bird carcasses, the introduction of quarantine and thorough disinfection of all premises and equipment. It is also necessary to introduce restrictions on the movement of live poultry and poultry products, both within a locality or region, and on a wider scale, depending on the situation.

Strict restrictive measures are especially necessary for poultry farms and poultry farms, where the birds are kept indoors. Avian influenza viruses can be transmitted to farms through the presence of various bird species on their territory: pigeons, crows, sparrows and others. In some cases, the routes of transmission remained unclear, which may indicate yet unknown sources of infection. In these cases, speculation arises about the possible role of birds or the use of bird droppings as fertilizer.

Infection control measures are much more difficult to implement on individual farms. It is difficult to ensure the isolation of poultry from contact with wild birds, especially in water bodies. Indeed, in the summer, all poultry in villages walks on water or lawns, grazing around their homes in search of food. This is especially dangerous when grazing domestic ducks or geese. In addition, even with successful attempts to isolate poultry, the problem of feeding it arises.

In addition to the difficulties of control, outbreaks of influenza in households carry a high risk of human exposure to the infection. Cases of infection of children who played in areas significantly contaminated with bird feces have been described. Infection can occur through water contaminated with bird feces. Therefore, caution is necessary when bathing and consuming raw water. Cases of infection of fighting rooster owners have been observed in Thailand. In households, it is not uncommon for sick birds to be slaughtered for food. This creates a dangerous situation during poultry slaughter, feather removal, carcass cutting and food preparation. For example, in Turkey in February of this year, 2 children who were tasked with slaughtering sick chickens became infected and died.

It is known that many birds breed in northern territories and fly south for the winter. Bird flights can neither be canceled nor banned. The migration of many millions of birds can be compared to a giant pump, twice a year pumping bird-adapted pathogens of various diseases from continent to continent. With the beginning of spring, birds flocked north, and the list of countries involved in the influenza epic immediately expanded significantly. As of February 21, it looked like this (in order of registration of the H5N1 virus): Iraq, Azerbaijan, Bulgaria, Greece, Italy, Slovenia, Iran, Austria, Germany, Egypt, India, France. This list has changed significantly since then.

Is the H5N1 virus easily transmitted from birds to humans? Fortunately, no. As noted, the reported number of human cases is negligible compared to the number of birds affected by this virus. It was unclear why some people became infected and became ill while others did not. Data has just emerged that explains this fact. It turned out that in humans, epithelial cells sensitive to the H5N1 influenza virus are located in the deepest parts of the lungs, almost around the alveoli, where oxygen exchange takes place. Therefore, coughing or sneezing is unlikely to release the virus from an infected person. But in the future, as the virus adapts to the human body, it will acquire the ability to infect other parts of our respiratory system, which will facilitate its spread from person to person.

What is the risk of a flu pandemic? It can begin if three conditions are met. The first is the emergence of a new subtype of influenza virus. The second is cases of infection of a person with a severe course of the disease. The third is the ability of the virus to spread easily from person to person. The first two conditions are already present. The H5N1 virus has never before circulated in nature, including among humans. Humans have no immunity to this virus. Thus, the only issue is the ability of the virus to quickly spread from person to person. The risk of this virus acquiring this capacity will remain whenever human cases are observed, which in turn depends on its circulation among domestic and wild birds.

What changes are needed for the H5N1 virus to become pandemic? The virus can increase its transmissibility among people through two mechanisms. The first is the exchange of genetic material during simultaneous infection of a person or pig with a human and avian virus. The second is a stepwise process of adaptive mutations that enhance the virus’s ability to infect human cells. Adaptive mutations appear initially in small outbreaks of human disease with established cases of person-to-person transmission of the virus. The recording of such cases will be a signal for active preparations for the pandemic and for putting plans in place to reduce its devastating consequences.

With the spread of the H5N1 virus outside of Southeast Asia, there is an increase in the number of cases of human infection from domestic and wild birds. Each new human infection gives the virus the opportunity to increase its transmissibility among people, leading to the emergence of a pandemic strain. When and where this will happen is impossible to predict, but it will inevitably happen.

Academician of the Russian Academy of Medical Sciences O. KISELEV, Director of the Influenza Research Institute of the Russian Academy of Medical Sciences (St. Petersburg).

Lately there has been a lot of talk and writing about bird flu. A dangerous virus is roaming the planet. Reports of new and new foci of the disease among birds are coming from Turkey, then from Romania, then from the south of Russia... Even people far from medical science, in the face of the threat of an influenza pandemic, began to become interested in epidemiology, virology and immunology.

Oleg Ivanovich Kiselev.

H5N1 avian influenza virus (shown in yellow) growing in cell culture. Recently, it is this virus that has caused surges in the incidence of influenza among migratory and domestic birds.

Schematic representation of influenza A virus. The genome of the virus consists of eight RNA segments. Influenza A virus subtypes differ in the variants of hemagglutinin HA (16 variants) and neuraminidase NA (9 variants).

Classification of influenza A viruses by two surface antigens (hemagglutinin HA and neuraminidase A) and the types of animals and birds - intermediate and final hosts of these types of viruses along the path of transmission to humans.

Field hospital for patients with influenza. USA, 1918.

The spread of bird flu, according to WHO, as of October 2005. Areas where outbreaks have occurred among poultry are shown in red.

Disinfection of a train traveling through areas where quarantine was introduced due to bird flu. Bucharest, 2005.

The magazine has already written about the classification and structure of influenza viruses, about the characteristics of bird flu and the ways of its spread, about the causes of pandemics among people. (See the article by Corresponding Member of the Russian Academy of Medical Sciences N. Kaverin “Variable Influenza”, “Science and Life” No.) Readers of the magazine, in their letters to the editor and questions sent to the “Science and Life” website, ask to explain the reasons for the emergence of a new virus, why flu among birds has become widespread and how dangerous avian epidemics are for humans. The director of the St. Petersburg Institute of Influenza of the Russian Academy of Medical Sciences, Academician of the Russian Academy of Medical Sciences Oleg Ivanovich Kiselev, answers these and other questions that concern many. The conversation is conducted by the head of the medicine department of the Science and Life magazine, Candidate of Chemical Sciences O. Belokoneva.

Academician of the Russian Academy of Medical Sciences O. KISELEV, Director of the Influenza Research Institute of the Russian Academy of Medical Sciences (St. Petersburg). - Recently, outbreaks of influenza among birds have become widespread. Have similar epidemics happened before?

Birds became carriers of influenza viruses millions of years ago. We can say that they are the reservoir of all influenza viruses of subtype A that exist in nature. They do not have subtype B virus. The bird "reservoir" has developed genetically as a result of evolution.

Avian influenza viruses were isolated back in the 30s of the last century; their evolution is seriously studied by specialists in environmental virology in our country and abroad. Doctors know the genealogy of these viruses, their genome, and properties. Large collections of non-pathogenic - non-hazardous to humans - avian viruses have been collected. The “regular” bird flu virus is not transmitted from birds to humans or from person to person. But from time to time the “reservoir” produces variants that are dangerous to people. By the way, studying the origin of animal and human influenza viruses has shown that they all have one evolutionary source - avian influenza viruses.

What must happen to an avian influenza virus for it to become pathogenic to humans? What are the mechanisms of “degeneration” of the bird flu virus into a “human” one?

The traditional viral chain begins with wild waterfowl. It has been established that they are carriers of all 16 subtypes of influenza A viruses, and the most primitive combinations of surface antigens (hemagglutinin HA and neuraminidase NA. - Note ed.) these viruses have up to 254. Every year, migratory birds generate different variations of the influenza A virus in their bodies. And this is at a body temperature of 42.5 o C. That is, the bird flu virus survives in conditions under which a person is already in a semi-fainting state.

Stopping in ponds with stagnant water, migratory birds introduce a virus with feces that can live up to 400 days - naturally, at optimal temperatures - from 10-12 to 30 o C. The virus is transmitted through water to waterfowl, and from it to other domestic birds feathered. Turkeys and chickens are most susceptible to infection. The influenza virus can then spread to pigs, which already poses a threat to humans. The fact is that on the surface of the pig cell membrane there are two types of receptors to which the influenza virus can attach: one is the avian version, and the other is the human one. And exactly half and half. Therefore, the pig can become an intermediate host for both avian and human influenza viruses. When two viruses—a human and an avian—infect the same cells, the progeny of those viruses inherit sets of RNA segments from both viruses. And as a result of their interpenetration (reassortment), sometimes a third highly pathogenic individual of the virus is born, capable of overcoming interspecies barriers and being transmitted to humans and birds. It is no coincidence that, according to statistics, the number of deaths from influenza is high if a person becomes infected in a rural area.

In addition, the avian influenza virus itself undergoes constant mutations of genes that determine the so-called host range. These are hemagglutinin (HA) genes, which control the entry of the virus into the host cell, and internal virus genes, which are directly responsible for suppressing the host’s immunity. As a result of these mutations, a virus dangerous to humans may also appear.

-Why are almost all human cases of avian influenza reported in Southeast Asia?

Southeast Asia combines high population densities with intensive livestock and poultry farming. These are very favorable conditions for the variability of influenza viruses. As a result, the avian influenza virus began to overcome interspecies barriers - both animals and people began to get sick from it. It is interesting that in the Central Asian region, where there is an intensive exchange of influenza viruses between wild migratory birds and domestic animals, but due to cultural and religious traditions, there is no pig farming, and the likelihood of the emergence of pandemic viruses is much lower than, for example, in China.

Were the influenza viruses that caused the pandemics of the twentieth century (in 1918, 1957, 1968) of avian origin or human?

All pandemic viruses of the 20th century contained avian influenza RNA segments to varying degrees. We can say that they had a "bird trail".

Over the past two years, about 140 cases of human infection with the H5N1 avian influenza virus have been reported worldwide, half of which were fatal. Is the H5N1 bird flu virus purely avian or partly human?

This is a purely avian virus, but it is constantly changing, adapting more and more to the human body. Still, I think that this virus will not cause a flu pandemic among people. To become pandemic, it must undergo major changes - reassortment or additional mutations. After all, as I already said, all pandemic viruses of the 20th century contained both avian and human RNA segments.

There is a fairly widespread belief that the threat of bird flu is an artificially inflated “horror story” that benefits large transnational poultry and pharmaceutical companies. How can you comment on this?

The H5N1 virus of 2004-2005 has indeed changed and become more dangerous than before. This is evidenced by such a large number of dead poultry. As a result, the risk of people getting sick increases. In 1997, the first outbreak of the epidemic among birds in Hong Kong was localized due to the fact that the entire population of poultry in the country was destroyed. Now it is impossible to do this - the virus has spread throughout Asia. And simultaneous outbreaks of bird flu in Japan, China, Vietnam, Thailand, Russia, and Kazakhstan are historically unprecedented. There is fear that a new strain of bird flu virus could affect the entire world.

So far, the virus has not been transmitted from person to person, but due to the epidemic among birds, such transmission is becoming increasingly likely. All that is needed is the “correct” recombination between the H5N1 strain and the human influenza virus. This can happen if any people or animals become sick with human and bird flu at the same time. Once an avian virus gains the ability to spread from person to person, a pandemic may begin, since there is little or no immunity to avian viruses in the human population. The results of recent studies indicate that the Spanish flu of 1918 claimed more than 40 million lives because that influenza virus evolved from an avian influenza virus and contained unique antigen proteins (HA and NA), to which humans had no immunity. In addition, it has been reliably established that a number of internal proteins of the Spanish flu virus, also of avian origin, had an outstanding ability to suppress human immunity.

The avian influenza virus can persist for many years at temperatures below _70 o C. Consequently, the risk of virus persistence in chilled and frozen poultry meat increases. But, fortunately, there cannot be an infectious virus in fried chicken meat or after cooking. Interestingly, the virus absolutely cannot withstand the procedure of sequential freezing and thawing.

What happened in the fall of 2005 in the Russian regions, when the death of the bird population became an epidemic, forced our scientists to sound the alarm. So the threat of a surge in the incidence of bird flu among people is a reality, and not a horror story invented by someone.

If the H5N1 virus is not likely to become a pandemic, then why are all the avian flu vaccines now based on it?

All countries are required to have this vaccine as a backup in case of mass spread of this particular type of bird flu. And when a new virus appears, then there will be a new vaccine. This always happens with influenza problems. Every year we analyze the situation and propose new vaccine compositions. Vaccine strains change on average every two to three years. Maybe in a year or two a new candidate will emerge based on a different strain of bird flu virus.

-The Influenza Research Institute has developed a new vaccine against bird flu. Tell us about her.

In fact, the vaccine was developed within the framework of the World Health Organization. Today, it is impossible to quickly solve the problem of creating a vaccine without collaborating with foreign scientists, without healthy corporate spirit. The major H5N1 core strain was obtained from the John Wood National Institute for Biological Standards and Control in London. This work was published in Nature in the middle of last year. Last summer we studied the virus as a candidate vaccine strain. And in August, at a meeting with the chief sanitary doctor of Russia, they came to the conclusion that it was necessary to prepare a vaccine based on this strain and put it into production. Similar vaccines are being created in other countries. Thus, the Americans have already launched the bird flu vaccine into production. They are now preparing to produce a new vaccine from the Indonesian isolate. And in Russia, due to the fault of the manufacturers, the timing of the release of the bird flu vaccine has not yet been determined.

Why can’t we construct a universal vaccine against all possible combinations of influenza virus antigens?

There are already several projects in the world for a universal flu vaccine. In terms of complexity, such a project is comparable, if not with a flight to Mars, then with something close to it. And our institute is also working on this problem, and practically without any funding. I think that if we have the money, we can make such a basic vaccine.

-Is it theoretically possible to make the human body invulnerable to influenza viruses?

It is quite possible to protect the human body from the influenza virus at the genetic level. But everyone knows that genetic manipulation of any kind on the human genome is strictly prohibited. And in relation to birds and animals, the likelihood of such an approach exists. For example, American geneticists propose to introduce into bird DNA genes encoding protein structures that neutralize antigenic molecules of the influenza virus (so-called antisense structures). If such proteins are present, the avian influenza virus will not be able to attach to host cells. As a geneticist by basic training, I can say that it is likely that humanity will have to take the path of genetic modification to ensure the safety of farm and wild animals.

-How can you protect yourself from flu, including bird flu, without vaccination?

For the prevention and treatment of influenza, including avian influenza, the Influenza Research Institute recommends domestic drugs included in the kit: “Human recombinant Interferon gamma” (“Ingaron”) and “Human recombinant Interferon alpha-2b” (“Alfarona”). The medicine is simply dropped into the nose. The kit can be purchased at a pharmacy without a prescription. I would especially like to emphasize that these drugs, created by Moscow scientists together with the St. Petersburg Research Institute of Influenza of the Russian Academy of Medical Sciences, exhibit high therapeutic activity in the avian influenza model. Only timely prevention of influenza can prevent the development of a severe course of the disease with an unpredictable outcome.

-How likely is it for a person to die if he does get avian flu?

Despite the danger of the virus, death from any influenza infection is an extraordinary event. First of all, you should consult a doctor in time and properly treat the infection. The likelihood of death from avian influenza largely depends on the health of the patient and on the organization of the health care system in the country. According to experts from the Influenza Research Institute, death from influenza in our time is an extraordinary event.

-Will poultry be vaccinated against bird flu?

The All-Russian Institute of Veterinary Poultry Science in St. Petersburg has developed, successfully tested and has now transferred to Rosselkhoznadzor for industrial production a highly effective vaccine for birds against the pathogenic influenza virus H5N1. The research was carried out jointly with the Influenza Research Institute, and the entire project was carried out solely on enthusiasm without funding from the state budget. This vaccine is still awaiting registration.

-Birds have many diseases. How to determine that chickens or ducks are dying from the flu?

Indeed, birds have many dangerous diseases even without influenza. To diagnose influenza in birds, WHO recommends immunofluorescence and PCR methods. In our country, avian influenza is diagnosed using immunological tests and determining pathogenicity in chickens. But these analysis methods take up to two weeks, and they also have low sensitivity and specificity. Now our employees and colleagues from the Institute of Bioorganic Chemistry named after M. M. Shemyakin and Yu. A. Ovchinnikov RAS in Moscow are developing a chip for the rapid diagnosis of avian influenza in birds. Moscow colleagues have synthesized the receptors of avian and human viruses, and here, at the Influenza Research Institute in St. Petersburg, specialists are creating the biochip itself, which looks like a small plate resembling a credit card, with built-in receptors for both types of viruses. With the help of such a device, any veterinarian in the regional center, having on hand the biomaterial of a dead bird, will be able to understand whether the avian influenza virus has affected the bird or whether it is another infection. Quick diagnosis is extremely necessary - the disease is insidious and fleeting.

Is there any data on the species composition of birds that carry avian influenza? Is it possible to get infected from birds during spring hunting?

Among wild migratory waterfowl, influenza virus carriers include wild ducks and geese, terns and plovers. But mainly avian influenza viruses have been isolated from wild ducks and geese. Great snipes, snipes and woodcocks do not get sick. Wood grouse, black grouse, hazel grouse too. I think the likelihood of infection from birds in central Russia is small. Most birds are not carriers of the influenza virus, so they should not be feared, much less destroyed.

-Why are there no reports of bird flu in the US?

There have been several outbreaks of avian influenza on US poultry farms. However, in this country the main producers of poultry meat are small factories with thirty to fifty thousand birds. We have poultry complexes with a population of millions of birds. If, for example, ten to twenty thousand animals die on a farm in the United States, the farm is isolated, preventative measures are taken, and insurance is paid to the owners. And there is no national tragedy, and the resonance in society is minimal. Considering the scale of Russian poultry farms, the level of bankruptcy they suffer is monstrous. Such an out-of-the-ordinary event, naturally, will not be ignored by either the sanitary authorities or the press.

Rumor has it that bird flu is the latest US biological weapon, directed against Russia, China and the Asian region. What do you think of it?

When the human immunodeficiency virus was discovered, the Pravda newspaper published a rather large article stating that HIV was synthesized in Pentagon laboratories. I declare with full responsibility: humanity has not yet matured enough to create such “genetic machines”. It is possible to enhance the pathogenic properties of the virus, preserve them and turn the finished virus into a bacteriological weapon. But scientists cannot yet identify the carrier of the virus, for example a duck: whether the virus takes root in it or not is from the evil one.

Actually, the question is correct. In the future, there may be “smart people” who will seriously engage in this kind of “work.” But for now, I am sure, this is completely ruled out. By the way, it is difficult to deceive scientists: even if something artificial appears, then specialists, having a clear understanding of the evolutionary development of viruses, will recognize a man-made infection immediately.