Should COVID-19 Vaccinated People Get a Flu Shot?

The annual flu vaccination campaign will start in September 2021. In this article, we will answer the main questions related to the seasonal epidemic of respiratory diseases and talk about the vaccines that are available to children and their parents this season.

Available: Ultrix quadri, Grippol Plus, Sovigripp and Flu-M.

Vaccine options

The first influenza vaccines were made from killed or neutralized viruses, they are called whole virion vaccines, as well as from attenuated strains, the so-called live vaccines.
Almost all modern vaccinations for the prevention of influenza are inactivated (killed) vaccines with a replaceable strain composition. Influenza viruses for all vaccinations without exception are grown on chicken embryos, which is reflected in the list of contraindications for vaccination. Most inactivated whole-virion influenza shots consist of purified and concentrated viruses cultured in chicken embryos that have been inactivated by formaldehyde or UV irradiation. Inactivated vaccines, in turn, are divided into whole-virion vaccines, which are based on undestructed whole influenza viruses; pre-killed and purified, split, or split vaccines, which include particles of destroyed virions, that is, the full antigenic composition (external and internal proteins). Subunit influenza vaccines are also used, which consist of a mixture of two viral proteins: hemagglutinin and neuraminidase. Therefore, these vaccines have a minimal number of adverse reactions.

Virosomal vaccines are a new technology in the production of vaccination material. These vaccinations contain an inactivated virosomal complex with surface antigens of the influenza virus. Virosomes enhance the immune response to vaccination. The virosomal vaccine does not contain preservatives (thiomersal) and is well tolerated.

In Russia, the following inactivated trivalent influenza vaccinations are mainly used: “Grippovac”, “Vaxigrip”, “Begrivac”, “Agrippal S1”, “Grippol”, “Grippol plus”, “Influvac”, “Fluarix”, “Inflexal V” ( virsomal vaccine). A total of 18 vaccinations have been registered in Russia.

Classification of trivalent influenza vaccines

Classification of quadrivalent influenza vaccines

Reactogenicity is the ability of a vaccine to cause any side effects when introduced into the body (fever, local swelling, etc.)

Vaccination

Most often, vaccination against influenza takes place in a clinic, but vaccination can be done in any other equipped institution if the patient wishes, for example, in a medical office of an enterprise, school, kindergarten, in a hospital, or a private medical clinic.

If the patient is at risk for possible influenza infection, vaccination should be planned and carried out in advance. On the eve of the start of the cold season (the potential season for the spread of the influenza virus - in late November - early December), such patients are invited to clinics, they are examined by a doctor, and then, if there are no health problems at the time of the examination, they are vaccinated.

If a person is not included in the risk group, but wants to independently protect himself from influenza vaccination, he needs to purchase any desired drug for vaccination and go to any medical institution, where he will be examined by a specialist and then given a referral for vaccination or undergo vaccination available for seasonal prophylaxis with the drug.

The flu vaccine is administered subcutaneously or intramuscularly into the deltoid muscle area. In the case of subcutaneous administration of the vaccine, the drug is injected into the area under the shoulder blade or into the shoulder. Some live vaccines can be administered intranasally by specialists.

It is important to remember that the risk category for influenza includes all children without exception.

However, vaccinating children against influenza has its own characteristics:

• young children can be given the flu vaccine no earlier than six months of age;
• Almost all flu vaccinations for young children are given twice;
• For children, the vaccine is administered only in the femoral area.

Such features are explained by the presence of maternal immunity in a child up to 6 months of age, and the need for revaccination a month later to strengthen immunity. The femoral area is optimal for anti-influenza vaccination in children due to the fact that if the body reacts to the administered drug, it is easiest to carry out resuscitation measures in this area (apply a tourniquet).

At the age when children attend kindergarten, they especially need a flu shot, since they do not yet have immunity to many diseases, and the large number of children contributes to the spread of a large number of infections. In the case of influenza, in this state of affairs, an outbreak of an epidemic of the disease is possible. The most ideal situation is when all members of the children's team are vaccinated against influenza. Together with them, all adults who are in constant contact with children - parents, brothers and sisters, teachers - should also be vaccinated. Before vaccinating a child, three days before, he should have minimal contact with third parties who can infect him with any infection. The same should be done for three days after vaccination - crowded places must be excluded from the child’s environment during this period of time. The most optimal situation is when the child, after vaccination, remains at home for a week under the supervision of his parents. If these rules are followed, stable specific immunity will be formed.

Principles and purposes of vaccination

Vaccination is especially important for people at higher risk of developing serious flu complications and for people who live with or care for people at high risk. WHO recommends annual influenza vaccination for the following population groups: pregnant women at any stage of pregnancy; children from 6 months to 5 years; seniors 65 years and older; people with chronic diseases; healthcare workers.

Since 2006, influenza vaccination has been included in the National Calendar of Preventive Vaccinations of the Russian Federation. The following are subject to annual vaccination: children from 6 months of age, children attending preschool institutions, students in grades 1-11, students of higher vocational and secondary vocational educational institutions, adults working in certain professions and positions (workers of medical and educational institutions, transport, public utilities and etc.), adults over 60 years of age.

It is important to note that the composition of vaccines changes every year. This is done to provide maximum protection against the “wild” influenza virus. This process is carried out under the control of the World Health Organization. It is she who predicts the strains of the flu virus that will circulate in the expected season and sends these strains to vaccine manufacturers. In most countries, influenza vaccination is carried out annually.

Vaccination during pregnancy and breastfeeding

Vaccination is the only method of safe and effective prevention of influenza in pregnant women, and has been performed in different countries for more than 20 years with inactivated split vaccines. This statement is based on a significant reduction in the prevalence, severity and consequences of influenza in pregnant women, with potential benefits for the babies they give birth to. According to WHO, pregnant women are a priority group to be vaccinated against influenza. This provision is based on a significant reduction in the prevalence, severity and consequences of influenza in pregnant women, with potential benefits for the babies they give birth to. Most experts agree that during the period of bearing a child, you can get vaccinated against influenza in the second or third trimester; it is better to try not to touch the first trimester.

In the case of a nursing mother, vaccination becomes a very necessary manipulation due to the fact that the body, weakened by childbirth, is more susceptible to infection by viruses. Even if enough time has passed after childbirth (several months), the immune system usually does not have time to restore itself due to the woman’s nervousness and lack of sleep. This may make a nursing mother more susceptible to influenza infection. By getting vaccinated, a woman will not only protect herself, but also protect her child from the virus, through the supply of antibodies produced from mother’s breast milk.

But flu vaccination is considered the most desirable and effective when planning pregnancy. During this period, the woman’s body is at the peak of its health, the immune system is not weakened in any way and is able to effectively form the necessary antibodies to any virus. It is important to avoid influenza during pregnancy, since its consequences can be very negative for the child, leading to intrauterine infection and even miscarriage.

High-quality and timely vaccination can save the health, and even life, of the mother and the unborn baby, so experts recommend thinking about vaccination when a woman is just starting to plan a pregnancy.

Vaccine effectiveness

The use of influenza vaccination reduces the incidence rate by 1.4-1.7 times, helps reduce the severity of the disease, and prevents the development of severe complications and deaths. The vaccine is effective in all age groups in approximately 70-90% of cases.

Immunization reduces hospitalizations for pneumonia by 40% in healthy adults and by 45 to 85% in older adults. In addition, the frequency of otitis media is reduced by 36-69%, exacerbations of chronic bronchitis by 20%, and the number of exacerbations of bronchial asthma is reduced by 60-70%. In organized groups of elderly people (nursing homes, boarding schools), mortality from influenza is reduced by 80%.

Immunity after administration of the vaccine is formed within 14 days and lasts throughout the season. Unfortunately, the immunity developed after vaccination is short-lived. This is largely due to the high variability of the circulating influenza virus, the emergence of a new or even the return of an old subtype of the virus. In this regard, the anti-influenza immunity developed in the previous year does not protect against the disease in the current year. Therefore, annual immunization is necessary using only the vaccine of the current year of production. Vaccinations with last year's vaccines are only 20-40% effective.

Benefits of vaccination

Scientists know more than two thousand types of influenza virus, and which of them will affect people in the coming year can only be guessed at. In addition, the virus is constantly mutating, forming new varieties. For this reason, there is an opinion that the flu shot does not help.

In fact, this argument does not mean that immunization is inappropriate. The effectiveness of vaccination is determined by several factors.

It is important not only to reduce the number of cases, but also to reduce the number of severe cases. After vaccination, the severity of symptoms and the duration of the disease are significantly reduced, and the risk of complications and deaths from influenza is significantly reduced. For this reason, WHO recommends vaccination for everyone who has no contraindications.

Opponents of immunization talk about a large number of complications after the introduction of the vaccine. However, the composition of drugs is updated annually, and modern vaccines are able to start the process of developing immunity with minimal side reactions and complications.

Materially, at the state level, vaccination also seems appropriate. Practice shows that the cost of developing and introducing drugs is less than the economic consequences of the spread of infection.

Post-vaccination reactions

Whole-virion influenza vaccinations are relatively highly reactogenic. Therefore, when using them, general reactions may develop in the form of increased body temperature, headache, weakness, as well as local reactions in the form of swelling, redness and pain at the injection site. Usually these reactions are mild and go away on their own.

Subunit, split, and virosomal vaccines are the least reactogenic of all flu vaccines. Only in 3% of cases are vaccinated people allowed to develop adverse reactions.

How does the vaccine work?

The effect of the influenza vaccine is not aimed at destroying the virus that already exists in the body. Vaccination is designed to mobilize protective immune functions, forming antibodies even before encountering the most common infectious disease.

The compositions of influenza vaccines can vary greatly due to the fact that their base can be either live or inactivated. Inactivated samples are artificially bred by cultivating the virus in a chicken embryo, then purifying it of impurities and rendering it harmless using ultraviolet rays or formaldehyde. The viruses used in vaccines are inactivated and do not cause influenza. However, mild side effects may occur, including a local reaction at the injection site. Live vaccines are whole-virion vaccines with viral virions, split protein-free, subunit vaccines with two viral proteins involved in the formation of an immune response to the virus in the body.

The period for administering the influenza vaccine must be chosen based on WHO forecasts regarding the upcoming epidemic, as well as on the instructions for the specific vaccine, which clearly states the period for developing the body's immune response. As a rule, this period ranges from 10 to 30 days.

The duration of the vaccine's effect also depends on the specific drug. Most often, antibodies to influenza are produced after vaccination for up to 6 months. However, in modern pharmacology there are drugs that protect health for 9-12 months.

Anti-influenza vaccination, subject to certain conditions, is the most effective method of protection against the disease. Experts include such conditions as maximum vaccination coverage of the population of all ages, the possibility of isolating sick people from other family members or team members, protection from contacts at the time of vaccine administration, when many come to the clinic and encounter already sick people before vaccination, high awareness of influenza vaccine prevention.

After using a subunit or split vaccine, the patient may experience a local reaction at the injection site for some time. It is completely normal and does not require medical attention as it goes away on its own. Such discomfort usually disappears within 2 days.

Flu vaccines have very low reactogenicity, meaning they rarely cause complications.

The individual characteristics of each human body can sometimes lead to such post-vaccination reactions as:

• allergy to the components of the drug;
• local reaction - infiltration at the injection site;
• the occurrence of mild catarrhal manifestations in the form of low-grade fever, sore throat and other symptoms that go away on their own within 2 days and occur only after the use of live vaccines.

In general, the presence of side effects is, in most cases, a normal reaction of the body to an antigen, reflecting the process of developing immunity.

Contraindications

For all influenza vaccines:

• hypersensitivity to chicken protein or any other component of the vaccine
• severe fever or allergic reactions after previous vaccination with influenza vaccines.

Influenza vaccination is postponed until the end of acute manifestations of the disease and exacerbation of chronic diseases. For mild ARVI, acute intestinal and other diseases, vaccination is carried out immediately after the patient has established a normal temperature.

The live vaccine is not used in children under 3 years of age, pregnant women and people with impaired immunity.

How is vaccination carried out?

Primary vaccination, if it is given to a child under 9 years of age, is a scheme of two procedures. The algorithm involves the implementation of a second injection, a month after the first. Experts recommend administering a second dose of the vaccine even if the procedure occurs at a time when the epidemic has already begun.

According to the instructions, intramuscular injection is required. The drug cannot be administered subcutaneously or intravenously; this administration technique will not give the desired result. For children under 3 years of age, the vaccine is injected into the thigh muscles, and for older patients - into the shoulder.

You can get vaccinated at a clinic or any institution where there is a specially equipped room and permission to carry out such procedures. These include medical stations in businesses, schools and preschools, as well as treatment rooms in hospitals. In addition, vaccination can be done for a fee at a non-state clinic.

Beautiful and with thorns: how the influenza virus works

If you look at the influenza virus under an electron microscope, you can see a rather cute ball with spikes. Any virus, in fact, is a hereditary material (DNA or RNA) packaged in a protein “case” of varying degrees of complexity. Flu is no exception. The RNA gene is hidden under the membrane envelope of the influenza virus, and two types of “spikes,” or surface antigens of the influenza virus, hemagglutinin (H) and neuraminidase (N), rise above the envelope.

When we see names of influenza strains, like A(H1N1) or A(H3N2), the H and N are the designations for hemagglutinin and neuraminidase. It is these two proteins that determine such properties of the influenza virus as immunogenicity and variability.

In simple words, the work of these proteins can be described as follows: hemagglutinin ensures the attachment of the virus to the cell, and neuraminidase is responsible for the ability of the viral particle to penetrate the host cell and exit it after reproduction. Some antiviral drugs actually suppress the work of neuraminidase so that viral particles cannot migrate into new cells.

Hemagglutinin is the main component of influenza vaccines, as it induces the formation of protective antibodies in the human body. The complex three-dimensional structure of this protein contains areas that are very important from the point of view of flu prevention - these are the so-called antigenic domains. When antibodies are formed, they block precisely these areas and make it impossible for the virus to enter the cell. But the influenza virus tries by any means to deceive the human immune system. Various types of mutations occur in the structure of its surface proteins, which lead to changes in the properties of the virus, or its drift.

Neuraminidase also changes. It is possible to change one or two antigens at the same time. Currently, 18 subtypes of hemagglutinins (H1 – H18) and 11 subtypes of neuraminidases (N1 – N11) are known.

There are a lot of variants of the influenza virus, they are divided into types: A, B, C. Influenza A viruses are the most dangerous, since they are responsible for pandemics and severe epidemics. These pathogens are more pathogenic and contagious than influenza viruses B and C. The fact is that virus A contains two types of neuraminidase (N1, N2) and four types of hemagglutinin (H0, H1, H2, NZ), due to which it is more variable, and B viruses are not divided into subtypes (only two lines). Influenza C virus contains only hemagglutinin and does not contain neuraminidase. Influenza C viruses, unlike viruses A and B, do not cause epidemics; they only lead to mild and asymptomatic illnesses in children and elderly patients.

Currently, influenza viruses of subtypes A(H1N1) and A(H3N2) are circulating among people. The World Health Organization (WHO) tracks them closely, especially the notorious H1N1. In the 1914–1920s, it caused a global pandemic called the “Spanish flu,” which killed between 40 and 100 million people.

Immunoprophylaxis and treatment of influenza: successes and problems

Influenza and other acute respiratory viral infections (ARVI) are the most widespread and common human diseases. They account for more than 90% of all infectious diseases. ARVI is a group of diseases that includes influenza, parainfluenza, adenovirus, respiratory syncytial, rhinovirus, reovirus, side-, metapneumo-, coronavirus and other viral infections (more than 200 varieties), characterized by a short incubation period, short-term fever, intoxication and damage various parts of the respiratory tract.

According to WHO, about a billion people worldwide fall ill with ARVI every year. At the same time, along with mild and moderate forms that end in recovery, some patients experience complications leading to the development of severe acute respiratory infection (SARI), and often to death. In most cases, SARI is caused by the influenza virus. The special place of influenza in the ARVI group is due to the ability of the virus to undergo antigenic variability, which determines the high susceptibility of the population.

Influenza poses a serious threat to all humanity and is an infection without borders. Every year, up to 650 thousand people worldwide die from influenza. This figure indicates the heavy burden of influenza and its serious socio-economic consequences. It emphasizes the importance of preventing seasonal influenza epidemics and ensuring preparedness for pandemics. When influenza pandemics occur, the number of sick and fatal cases increases tens and hundreds of times. On a global scale, protection against this disease is effective only if the health care system of each country is ready to respond in a timely manner to an emergency.

There were influenza pandemics in 1918, 1957, 1968 and 2009. The world must prepare for a new influenza pandemic, it will happen, it’s a matter of time. The 2009 influenza A(H1N1) pdm/09 virus pandemic demonstrated the need to strengthen the response during inter-pandemic periods (during seasonal influenza) through improved surveillance, laboratory capacity, immunization coverage and communication, which are the basis for implementation more decisive measures to counter the pandemic.

The goal of the global influenza strategy for 2019–2030 is are the control of seasonal influenza and disease transmission from animals to humans, as well as preparation for the next pandemic, including the development of new ways to prevent, control and treat influenza [1].

Immunoprophylaxis of influenza

Of the entire spectrum of ARVI pathogens, only influenza has been developed with specific prevention, which plays a major role in reducing the incidence of influenza. Annual population vaccination is the best and most effective strategy for reducing influenza morbidity and mortality.

Benefits of flu vaccination:

• protects against disease;
• reduces the risk of complications associated with influenza infection in both children and adults, including the elderly;
• protects risk groups with concomitant chronic pathology from severe disease. Reduces the likelihood of hospitalization due to the development of pneumonia and other complications of influenza among people over 65 years of age;
• protects pregnant women and the fetus from influenza and its complications. Children born to vaccinated pregnant women are protected from influenza for 6 months after birth;
• significantly reduces mortality from influenza.

According to the Order of the Ministry of Health of Russia dated March 21, 2014 No. 125n “On approval of the national calendar of preventive vaccinations and the calendar of preventive vaccinations for epidemic indications,” persons belonging to categories of high risk of influenza disease and adverse complications of the disease are subject to vaccination against influenza, which include:

• children from 6 months, students in grades 1–11;
• students studying in professional educational organizations and educational organizations of higher education;
• adults working in certain professions and positions (employees of medical and educational organizations, transport, public utilities);
• pregnant women;
• adults over 60 years of age;
• persons subject to conscription for military service;
• individuals with chronic diseases, including lung diseases, cardiovascular diseases, metabolic disorders and obesity [3].

Vaccination in risk groups must be at least 75% of those vaccinated in order to provide effective protection. Achieving vaccination coverage of 40% or more makes it possible to control the course of influenza and reduce the incidence rate.

An analysis of the incidence of influenza in the population of the Russian Federation over the past 20 years has shown that immunoprophylaxis of influenza leads to a significant reduction in morbidity and mortality among the population. In Russia, since 1997, the incidence rate of influenza has decreased by 200 times (from 5173.8? in 1997 to 26.33? in 2021), which is mainly due to an increase in vaccination coverage of various population groups [2].

In 2021, flu vaccination coverage of the country's population was 49%; 70.8 million Russians were vaccinated against influenza (Fig.).

According to the WHO global immunization report for 2018, the coverage rate for influenza vaccination in Europe is 41.8%, in the USA - less than 44.9% in adults and 45.6% in children, the coverage rate for vaccination for flu prevention in Russia is 49%.

Global production capacity for influenza vaccines is approximately 500 million doses per year, and the global need for influenza vaccines, in accordance with the 2003 WHO resolution, is approximately 5.7 billion doses.

Vaccine prevention of influenza is not only preventing the spread of the disease, reducing the number of severe forms and mortality, but also a factor in reducing the economic costs of healthcare to combat annual influenza epidemics.

Among all infectious diseases, influenza ranks first in terms of economic damage - over 75–80% of all losses associated with temporary disability and the cost of treating patients. Depending on the strain, financial losses range from 15–20% of the revenue for the same period of a business entity affected by the epidemic. In 2021, according to WHO, influenza “wasted” more than $10 billion globally.

In Russia, the average cost of treating one patient with influenza in the regions of the country is about 3 thousand rubles, in Moscow - up to 4–5 thousand rubles. In recent seasons, according to Rospotrebnadzor estimates, Russia is losing from 1.7 to 2.1 billion rubles [6, 7].

Mass free influenza vaccination under the compulsory medical insurance program began in Russia in 2006 with the inclusion of the influenza vaccine in the National Calendar of Preventive Vaccinations. For many years, the Russian Ministry of Health and Rospotrebnadzor have consistently pursued a policy to expand vaccination coverage among the population.

In order to improve the system of prevention and control of morbidity and mortality from influenza, as well as assess the effectiveness of domestic vaccines against influenza, within the framework of a project of the Russian Ministry of Health, since 2015, monitoring of immunization, morbidity and deaths from influenza has been carried out in accordance with the Order of the Russian Ministry of Health dated October 27, 2015. No. 755n “On approval of statistical registration form No. 1-influenza “Information on acute respiratory viral infections, including influenza, and the procedure for filling it out.” New technologies are used for transmitting data from information centers of the constituent entities of the Russian Federation, collecting and processing data, and improving statistical forms. Since 2021, the revised program has been included in the Uniform State Health Information System information system.

According to immunization monitoring data, influenza immunization coverage among risk groups has increased significantly since 2015 (Table 1).

One of the main tasks of healthcare is to increase public confidence in influenza immunoprophylaxis. Thanks to the pro-vaccination campaign, adherence to immunization has significantly increased among children and people over 60 years of age.

It should be noted that immunization coverage among pregnant women is very low. Pregnant women are at high risk of developing complications and mortality from influenza. Influenza in a pregnant woman, when infected in the first trimester, leads to the most unfavorable outcomes. It is known that the frequency of spontaneous miscarriages increases by 25–50%, premature births by 15–20%, chronic hypoxia and fetal growth restriction syndrome by 7–10%, etc. The likelihood of transplacental transmission of the influenza virus is high. Malformations are registered 5 times higher among children born to women who had the flu in the first trimester, compared to those who fell ill in the second and third trimester. The solution to the problem is to train medical workers to effectively communicate with doubtful patients, and to widely and systematically provide reliable information about the effectiveness of vaccination.

Since 2015, the number of vaccinated population has increased annually, from 44.9 million people in 2015 to 70.8 million people in 2018. The number of those vaccinated as part of the implementation of the National Preventive Vaccination Calendar (NCPP) also increased, with 39.46 million people in 2015 to 62.3 million people in 2021. It should be noted that for seasonal influenza vaccination within the framework of the NCPP, exclusively domestically produced inactivated influenza vaccines were used (Table 2).

The highest levels of influenza incidence among the total population were recorded in the 2015–2016 season. (50.38 per 100 thousand population) and the lowest rates of 16.67 per 100 thousand population were in 2017–2018. At the same time, the incidence of influenza among vaccinated people did not exceed 2.98 per 100 thousand population, i.e., the incidence of influenza among vaccinated people during these four epidemic seasons is on average 15 times lower than the general incidence of influenza in the country (Table 3) .

At present, there is no doubt that effective control of influenza is possible only through mass immunoprophylaxis.

Russia is the seventh country in the world to have its own independent production of such vaccines. In 2021, the inactivated subunit adjuvant vaccine Grippol® Quadrivalent was registered.

In 2021, the Russian Federation released a quadrivalent inactivated split influenza vaccine Ultrix® Quadri, containing two antigens of the influenza virus type A (subtypes A (H1N1) and A (H3N2)) and type B (Yamagata line and Victoria line). A key feature of the vaccine is that it contains, in accordance with WHO recommendations, 15 mcg of hemagglutinin of each strain in one dose; in total, one dose contains 60 mcg of antigens. The active substances - influenza virus antigens - are obtained from purified influenza viruses type A and B, grown separately in developing chicken embryos. The vaccine does not contain preservatives, adjuvants or immunomodulators. A Russian drug with such a composition and antigen content is the first registered in the Russian Federation (RU No. LP-005594 dated June 19, 2021).

A study of the immunogenic activity of the quadrivalent inactivated split vaccine for the prevention of influenza Ultrix® Quadri showed that the vaccine meets the immunogenicity criteria for inactivated influenza vaccines adopted in the European Union and the Russian Federation.

Indications for use of the Ultrix® Quadri vaccine are active annual preventive immunization against seasonal influenza for people aged 18 to 60 years. The vaccine is especially indicated:

1) persons at high risk of illness and complications in case of influenza:

• persons who often suffer from acute respiratory viral infections;
• persons suffering from chronic somatic diseases;

2) persons who, due to the nature of their educational or professional activities, have a high risk of contracting influenza or contracting it from other persons:

• employees of medical and educational institutions, transport, municipal and social spheres, police, military personnel, etc. (“Instructions for the medical use of the drug Ultrix® Quadri”, Ministry of Health of Russia LP-005534–190610 dated 06/19/2019).

In 2021, it is planned to expand the recommended population of vaccinated individuals by amending the instructions for use of the Ultrix® Quadri vaccine upon completion of clinical studies to study tolerability, safety and immunogenicity in children and pregnant women.

The effectiveness of this vaccination is expected to affect the incidence of influenza, especially for influenza B viruses, which have a much lower rate of variation than influenza A viruses.

The Russian Ministry of Health and Rospotrebnadzor have developed a plan for the transition until 2023 from the use of trivalent influenza vaccines within the framework of the NCPP to the use of quadrivalent influenza vaccines.

Analysis of the effectiveness of the use of domestically produced vaccines in vaccination companies 2015–2019. allows us to draw conclusions.

• According to monitoring of influenza immunization, morbidity and deaths from influenza, the incidence of influenza in the unvaccinated population is 15–20 times higher than in the group vaccinated against influenza within the framework of the NCPP. This indicates the high effectiveness of the vaccines.
• Annual immunization against influenza, covering at least 40% of all social and professional groups of the population, is an effective way to reduce the number of severe forms of disease and mortality.
• Vaccine prevention today is not only preventing the spread of the disease, reducing mortality, but also combating drug resistance, as well as a factor in reducing economic costs, etc.

Diagnosis and treatment of influenza

Diagnosis of influenza in adults is made by collecting an epidemiological and clinical history, clinical examination, laboratory and special examination methods and is aimed at determining the clinical form, severity of the condition, identifying complications and indications for therapy. During periods of epidemic rises in incidence, the final diagnosis of “influenza” can be established both on the basis of laboratory confirmation and on the basis of clinical and epidemiological data. The medical history should take into account contacts with infectious patients, timeliness of seeking medical help, and taking initial antiviral therapy [4].

Clinical features of influenza:

• sudden onset of illness;
• severe intoxication;
• high body temperature;
• Strong headache;
• severe: myalgia, arthralgia, pain in the orbital area;
• the injection of scleral vessels is pronounced;
• damage to the respiratory tract - mainly tracheitis;
• dry hacking cough;
• catarrhal manifestations are not expressed (soreness along the trachea, sore throat);
• bright hyperemia of the oropharynx with a cyanotic tint of the soft palate.

Laboratory research:

• clinical blood test with determination of the leukocyte formula. Influenza is characterized by normo- or leukopenia, and with the development of bacterial complications - leukocytosis;
• clinical urine analysis. With uncomplicated influenza, moderate proteinuria and slight erythrocyturia are possible.

Instrumental studies:

• pulse oximetry at all stages of medical care for patients with influenza for early diagnosis of respiratory disorders in complicated course of the disease;
• X-ray of the chest organs if pneumonia is suspected;
• ECG in the presence of cardiac symptoms, concomitant cardiovascular and bronchopulmonary pathology. For uncomplicated forms of influenza, studies are not prescribed.

Specialist consultations:

• otorhinolaryngologist (if the development of sinusitis, otitis is suspected);
• infectious disease doctor (for severe and moderate influenza, patient refusal of hospitalization, group cases of the disease).

For uncomplicated forms, consultations are not carried out.

The goal of influenza treatment is a rapid and complete clinical recovery of the patient.

Main goals of therapy:

• suppression of viral replication in the early stages of the disease;
• relief of clinical manifestations of viral infection;
• prevention and treatment of complications, when justified, competent, timely use of antibiotics and pathogenetic drugs is necessary.

The timing of initiating treatment for patients with suspected or probable cases of influenza does not depend on the lack or delay in obtaining the result of diagnostic testing for influenza.

Mild and uncomplicated moderate forms of influenza are treated on an outpatient basis. A patient undergoing outpatient treatment should be advised to seek medical help if the condition worsens or symptoms persist for more than 3 days without a tendency to improve.

Hospitalization is carried out in severe forms and progressive or complicated course of the disease.

Indications for emergency hospitalization in the infectious diseases department:

• influenza with severe and moderate course;
• suspected pneumonia;
• signs of acute respiratory failure;
• lack of effect from outpatient treatment;
• according to epidemiological indications in the absence of the possibility of isolation (accommodation in a hostel, hotel, etc.);
• with exacerbation or decompensation of concomitant diseases of the cardiovascular system and respiratory system, metabolic disorders (diabetes mellitus, obesity of II–III degree), diseases of the gastrointestinal tract, chronic renal or liver failure, severe body weight deficiency.

It is recommended to hospitalize pregnant women (at any stage and in the postpartum period), persons over 65 years of age, and patients with malignant neoplasms.

Modern approaches to influenza treatment involve the use of both drug and non-drug methods.

Non-drug treatment:

• strict bed rest for the entire febrile period;
• carrying out hygiene measures;
• plenty of warm drinks for the entire febrile period;
• rational nutrition (easily digestible foods: dairy-vegetable diet; fruits, vegetables);
• physical methods of reducing temperature, sanitation of the upper respiratory tract (nasal passages), rinsing the oropharynx, physiotherapy.

Drug treatment

For the treatment of influenza, WHO recommends the use of chemotherapy drugs that block the replication of the virus, that is, those that have a direct antiviral effect. In this case, antiviral therapy should be prescribed as early as possible, from the moment of the first symptoms (in the first 48 hours of illness), and begin without waiting for laboratory verification of the diagnosis. These recommendations apply to all patient groups, including pregnant women, young children, the elderly, and patients with underlying health conditions (Table 4).

The advantages of timely administration of antiviral therapy are a reduced risk of complications, shortening the period of fever and other symptoms, which has been clinically proven. Antiviral therapy is indicated even when patients seek medical help late.

In the Russian Federation, direct antiviral drugs include neuraminidase inhibitors (oseltamivir and zanamivir), hemagglutinin inhibitor and fusion inhibitor (umifenovir), and virus M2 channel blockers (rimantadine, amantadine).

Oseltamivir and umifenovir have proven effectiveness and are included in the list of vital and essential drugs (VED) and current recommendations for the treatment and prevention of influenza approved by the Russian Ministry of Health [4] (Table 5).

The use of neuraminidase inhibitors in some cases has its own peculiarities (Tables 6, 7).

Management tactics for patients with severely complicated influenza

In case of severe clinical condition, emergency hospitalization in an infectious diseases hospital is mandatory!

• Prescribing specific antiviral therapy not only in the first 2 days, but also later (after the 3rd day of illness, etc.).
• If pneumonia is suspected, broad-spectrum antibiotics are immediately prescribed.
• Careful clinical observation in the infectious diseases department. If there are signs of deterioration, transfer to an intensive care unit or intensive care unit.
• Dynamic X-ray or computed tomography according to clinical indications.
• Express monitoring of blood gas composition over time.
• Providing continuous respiratory support with oxygen, including artificial ventilation.
• Extracorporeal membrane oxygenation (ECMO).
• The use of corticosteroids and specific immunoglobulins.

Pathogenetic therapy for ARVI, including influenza, is represented by drugs, the use of which is possible in combination and in the presence of severe intoxication and febrile fever [8] (Table 8).

Thus, therapy for patients with influenza should be comprehensive. It is necessary to start treatment as early as possible. The maximum clinical effect can be obtained only with the combined use of drugs of different pathogenetic directions:

• antiviral (etiotropic);
• immunotropic;
• detoxification (to relieve intoxication syndrome);
• symptomatic (antipyretics, antihistamines);
• expectorants, antitussives;
• antibacterial (for bacterial complications).

The principle of treating influenza is “the sooner the better.” Initial antiviral therapy in the early stages of the disease is carried out to suppress the replication of the influenza virus.

Reducing the viral load is the prevention of complications.

Complex therapy (antiviral and antibacterial) for complicated influenza contributes to a more favorable course of the disease.

Conclusion

In recent years, extensive experience has been accumulated in immunoprophylaxis, diagnosis and treatment of influenza. The data presented remind us of the seriousness of the influenza problem and that influenza prevention should be a global priority in all countries.

The team of authors hopes that these data will be useful to medical doctors in developing adherence to influenza vaccine prevention, as well as the importance of choosing etiotropic therapy and timely provision of medical care to patients with influenza.

Literature

1. www.who.int.
2. rospotrebnadzor.ru.
3. Order of the Ministry of Health of the Russian Federation dated March 21, 2014 No. 125n “On approval of the national calendar of preventive vaccinations and the calendar of preventive vaccinations for epidemic indications.”
4. Federal clinical guidelines “Influenza in adults”, 2017.
5. SP 3.1.2.3117–13 “Prevention of influenza and other acute respiratory viral infections.”
6. Briko N. I., Saltykova T. S., Gerasimov A. N., Suranova T. G., Pozdnyakov A. A., Zhigarlovsky B. A. Clinical and epidemiological characteristics of influenza in 2015–2016 and 2016–2017. // Epidemiology and infectious diseases. Current issues. 2021. No. 4. pp. 4–13.
7. Zhigarlovsky B. A. Temporary disability due to influenza and ARVI in the Russian Federation and Moscow // Epidemiology and vaccine prevention. 2021. T. 18. No. 3. P. 4–12.
8. Orlova N.V., Suranova T.G. Modern approaches to the treatment and prevention of acute respiratory viral infections // Medical alphabet. 2021, No. 21, vol. 2, p. 35–40.

N. I. Briko*, 1, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences V. V. Nikiforov**, Doctor of Medical Sciences, Professor T. G. Suranova***, Candidate of Medical Sciences N. A. Polezhaeva*** * T. S. Saltykova*, Candidate of Medical Sciences

* Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after. I. M. Sechenov Ministry of Health of Russia, Moscow ** Federal State Budgetary Educational Institution of Higher Education Russian National Research Medical University named after. N.I. Pirogova Ministry of Health of Russia, Moscow *** Federal State Budgetary Institution Federal Scientific Center FMBA of Russia, Moscow **** Federal State Institution MNIIEM named after. G. N. Gabrichevsky Rospotrebnadzor, Moscow

1 Contact information

DOI: 10.26295/OS.2019.41.60.009

Immunoprophylaxis and treatment of influenza: successes and problems / N. I. Briko, V. V. Nikiforov, T. G. Suranova, N. A Polezhaeva, T. S. Saltykova For citation: Attending physician No. 12/2019; Page numbers in the issue: 53-58 Tags: immunoprophylaxis, acute respiratory diseases, influenza virus

"Nacimbio" guarding the country's immunity

In the epidemic year 2019-2020. in the Northern Hemisphere, according to WHO, the following strains will dominate: A/Brisbane/02/2018 (H1N1)pdm09; A/Kansas/14/2017 (H3N2); B/Colorado/06/2017 (B/Victoria-like line); B/Phuket/3073/2013 (B/Yamagata-like lineage). The first three are intended for trivalent influenza vaccines, the fourth is an additional strain for inclusion in quadrivalent vaccines.

WHO announces what types of influenza will threaten this year in advance, before the start of the epidemic season. For this purpose, the Organization has a network of laboratories - 149 National Influenza Laboratories in 121 countries, which during epidemics isolate strains from patients, study antigenic and genetic properties, and determine the most relevant ones. WHO specialists also analyze many other factors - the movement of people, the migration of birds. Based on all this information, a list of dangerous strains is predicted. This year, the WHO provided vaccine manufacturers with the current strains at the end of March, a month later than usual - experts for a long time could not determine which strain of the A/H3N2 virus should be included in the vaccines.

“I don’t think there will be any problems with the supply of drugs in Russia. We have quite a lot of enterprises whose capacity is enough to compensate for this WHO delay. There will be no shortage, we can produce the vaccine with reserves,” commented Anton Katlinsky, adviser to the general director of Nacimbio. This holding company, part of the Rostec State Corporation, is the only supplier of vaccines for the implementation of the National Calendar of Preventive Vaccinations in Russia.

In the 2018-2019 season. The Rostec pharmaceutical holding donated more than 62 million doses of vaccines produced entirely from Russian raw materials for the nationwide flu vaccination campaign. Despite the WHO delay, Nacimbio not only met the delivery deadlines for the first stage, but also plans to transfer the entire volume of drugs - at least 63 million doses of vaccines - two weeks earlier than last year.

To prevent influenza, Nacimbio supplies the Sovigripp vaccine, which is produced by NPO Microgen, FORT LLC and SPbNIIVS FMBA of Russia, and Ultrix, developed by Ryazan FORT. This season, a new quadrivalent vaccine, Ultrix Quadri, has also been added to the list.

In many developed countries today they are switching to a quadrivalent influenza vaccine, that is, containing two current strains A and two current strains of influenza B. The domestic quadrivalent vaccine was registered with the Ministry of Health in July 2021. This season, it will be used to vaccinate those at risk - social workers, transport and healthcare workers. Russia will switch completely to vaccinations with four strains by 2023. By the way, our country is the seventh in the world where a quadrivalent vaccine is produced in a full cycle.

ULTRIX QUADRI (Fort, Russia)

It is a vaccine against all four circulating seasonal influenza virus strains. The composition includes inactivated influenza viruses split into individual small antigens. Ultrix Quadri does not contain adjuvants, since the concentration of viral antigens in the drug is sufficient to form an immune response.

Intended for vaccination of children from 6 years of age and adults up to 60 years of age. Not yet approved for older ages.

Supplied in a pre-filled syringe.