Sinusitis

Active immunization against hepatitis B. Viral hepatitis B

Passive immunization is the introduction of antibodies to any antigens. Passive immunization can only create temporary immunity lasting 1-6 weeks. Although passive immunization causes a short-term increase in resistance to the pathogen, its effect is immediate. Repeated passive immunization does not strengthen immunity and is often accompanied by complications. Passive immunization is used to create temporary immunity after contact with an infectious agent in cases where active immunization for one reason or another is not carried out in advance (for example, against cytomegalovirus, against rabies). Passive immunization is also used to treat diseases caused by bacterial toxins (in particular, diphtheria), poisonous snake bites, spider bites, and for specific (anti-Rh0(D) immunoglobulin) and nonspecific (antilymphocyte immunoglobulin) immunosuppression.

For passive immunization, three types of drugs are used: - normal human immunoglobulins (outdated name - gamma globulin) for intramuscular or intravenous administration; - specific human immunoglobulins with a high content of antibodies against certain pathogens (for example, against the hepatitis B virus or against the varicella-zoster virus); - specific sera, including antitoxic ones, obtained from immunized animals.

Based on their origin, drugs are divided into homologous (made from human blood serum) and heterologous (from the blood of hyperimmunized animals). The first drugs are administered immediately in full dose, the second - according to the Bezredka method. First, 0.1 ml of normal horse serum diluted 1:100 is injected intradermally and the reaction is observed for 20 minutes. The test is considered positive if the diameter of the papule reaches 1 cm or more. If the intradermal test result is negative, the administration of serums begins with a subcutaneous injection of 0.1 ml, and if there are no reactions within 30 minutes, then the remaining amount of serum is injected intramuscularly. If the intradermal test is positive, serum is administered only for unconditional indications, i.e., if the patient’s life is threatened. In this case, a diluted serum is first administered subcutaneously, which is used to perform an intradermal test at 20-minute intervals in doses of 0.5, 2.0 and 5.0 ml, which leads to desensitization. If there is no response to these doses, then 0.1 ml of undiluted hyperimmune serum is administered subcutaneously, then after 30 minutes the entire prescribed dose is administered. If a reaction occurs to one of the doses of the therapeutic serum, it is administered under anesthesia, having a syringe with adrenaline or ephedrine ready. Based on the direction of action, drugs are divided into antitoxic, antiviral and antibacterial.

Antiviral Homologous immunoglobulins anti-rabies anti-rotavirus against hepatitis B anti-influenza against tick-borne encephalitis against cytomegalovirus Heterologous immunoglobulins anti-rabies against Venezuelan equine encephalomyelitis against tick-borne encephalitis against Ebola fever against Japanese encephalitis

Antibacterial Homologous immunoglobulins complex immunoglobulin preparation (CIP). KIP is a lyophilized protein solution containing immunoglobulins of the classes IgG, IgA, IgM, isolated from human blood plasma. Heterologous immunoglobulins lactoglobulin coliproteus antileptospirosis antianthrax

Immune serums Immune serums are preparations from animal and human blood containing antibodies against pathogens of infectious diseases or their metabolic products. During the preparation process I.S. The blood serum of animals or people (donors) immunized with certain antigens, or those who have recovered from the disease, is subjected to various treatments, depending on the type and purpose of the I.S.: purification, during which ballast substances are removed and active, primarily globulin, protein fractions are isolated. The administration of immune serum from animal blood to humans may be accompanied by complications (serum sickness, anaphylactic shock). Concentrated immune serums - gamma globulins from human blood - practically do not cause these complications and are eliminated from the body more slowly. Depending on the purpose, therapeutic-prophylactic and diagnostic immune sera are distinguished. Therapeutic and prophylactic immune sera are divided into antitoxic - against poisonous waste products of microbes (for example, antitetanus, antidiphtheria, antigangrenosis) and against the consequences of the bite of poisonous snakes and insects; antibacterial - affecting the microorganism (anti-anthrax gamma globulin) and antiviral (for example, anti-measles, anti-rabies, anti-influenza gamma globulins).

Immunoglobulins This type of immune preparations contains antibodies in finished form. They are used for therapeutic and prophylactic purposes, as well as for emergency prevention of infectious diseases. Immunoglobulins may have antimicrobial, antiviral or antitoxic effects. Immunoglobulin is obtained from placentas or donor blood. The latter is more purified and does not contain hormonal substances. The positive aspects of using immunoglobulins are that a ready-made set of antibodies is introduced into the body in a sufficient dose within a short period of time. At the same time, the drug is destroyed relatively quickly, suppresses the synthesis of its own immunoglobulin, and allergizes the body.

Normal human immunoglobulin (measles) is prepared from donor blood serum, as well as placental and abortion blood. It contains antibodies against the measles virus in a fairly high concentration, and antibodies against the causative agents of influenza, chickenpox, polio, rubella, whooping cough, diphtheria and many other bacterial and viral infections in various concentrations, because it is prepared from a mixture of a large number of adult sera that During their lifetime they could have suffered from various diseases or undergone various types of vaccinations.

Targeted immunoglobulins are prepared from the blood of people specially immunized against specific infectious diseases, as well as by collecting the blood of those donors who are determined to have elevated levels of antibodies to a specific pathogen without prior immunization.

Tetanus toxoid immunoglobulin Human tetanus immunoglobulin is a concentrated solution of a purified fraction of immunoglobulins isolated by ethyl alcohol fractionation from the blood plasma of donors immunized with tetanus toxoid. The active principle of the drug is class G immunoglobulins, which have the activity of antibodies that neutralize tetanus toxin. The maximum concentration of antibodies in the blood is achieved hours after administration; The half-life of antibodies from the body is 3-4 weeks.

Antistaphylococcal plasma Received at blood transfusion stations from donors immunized with staphylococcal toxoid. After immunization and the appearance of specific antibodies in the blood at a titer of 6.0 - 10 IU/l, donors undergo plasmapheresis. During plasmapheresis, a portion of blood is extracted from the body, which is then divided into plasma and formed elements, blood cells are returned to the body, and the removed plasma is used.

CHAPTER 19. VACCINES AGAINST HEPATITIS AND IMMUNOPREVENTION

1. What can you say about the development of the concept of immunization (vaccination)?

Over the past century, remarkable discoveries in microbiology have made significant progress in the treatment and prevention of infectious diseases. In 1798, Edward Jenner first published information about the use of smallpox vaccine. He found that people vaccinated and infected with the cowpox virus became immune to smallpox. E. Jenner called this procedure vaccination. This was the first time a vaccine was used to prevent the development of the disease. The word "vaccine" comes from the Latin word for "cow", because cows were the "hosts" of the virus used to make the first real vaccine.
The success of immunization is based on one main idea: humans have specific immunological mechanisms that can be programmed to protect the body from pathogens of infectious diseases. Stimulation of immune mechanisms is carried out through the direct administration of infectious agents or parts thereof in the form of a vaccine. The golden era of vaccination development began in 1949 with the discovery of viral reproduction in cell culture. The first patented product obtained using the new technology was Salk's trivalent formaldehyde-inactivated polio vaccine. Soon, vaccines were created against viral hepatitis A and B (the causative agents of which were discovered in 1973 and 1965, respectively).

2. What are the differences between active and passive immunizations?

Active immunization is based on the introduction of a specific antigen into the body, which stimulates the production of antibodies that prevent the development of the disease. Passive immunization, or immunoprophylaxis, is the administration of ready-made antibodies to prevent the development or alteration of the natural course of the disease in presumably infected individuals. Antibodies are obtained as a result of immunization of animals and people, and are also taken from the serum of those who have recovered from illness naturally.

3. List the main types of vaccines.

The classic method of producing vaccines is to modify the infectious agent so that the final product becomes suitable for use in humans. Currently, 2 types of vaccines are widely used: (1) inactivated (or killed) vaccines, which contain a pathogen that cannot reproduce in the host’s body, but retains antigenic properties and the ability to stimulate the production of antibodies; (2) live, attenuated vaccines prepared from viable but weakened microorganisms that cannot cause a full-blown disease. The end result of vaccination is the production of antibodies and prevention of disease development. Live vaccines usually contain relatively low concentrations of infectious agents. They are usually administered once, which provides long-lasting immunity. The immune response during vaccination with killed vaccines corresponds to the concentration of the antigen. Revaccination is often required to create long-lasting immunity.

Human vaccines


LIVE	KILLED	VACCINES CONTAINING PURIFIED PROTEINS (OR POLYSACCHARIDES)
Anti-smallpox (1798)	Anti-rabies	Containing diphtheria
Anti-rabies (1885)	(received recently)	toxoid (1888)
Against yellow fever (1,935)	Typhoid	Diphtheria (1923)
Poliomyelitis (Sabina)	Against Cholera (1896)	Tetanus (1927)
Measles	Anti-plague (1897)	Pneumococcal
Against mumps	Anti-Flu (1936)	Meningococcal
Against measles rubella	Poliomyelitis (Solka)	Against Hemophilus influenzae
Adenoviral	Against hepatitis A (1995)	Against hepatitis B (1981)
Against hepatitis A (under investigation)

4. What is immunoprophylaxis?

In immunoprophylaxis, or passive immunization, ready-made antibodies obtained as a result of immunization of animals and people or from the serum of those who have recovered naturally are used to prevent the development or change in the natural course of the disease in an infected person. Passive immunization provides only short-term protection for the body (from several weeks to several months). Immunoprophylaxis was considered the main method of preventing the development of viral hepatitis A and B until the advent of appropriate vaccines. Passive immunization can also occur naturally through the transfer of class G immunoglobulins from mother to fetus. Thus, the blood of a newborn contains a certain amount of maternal antibodies, which provide protection against many bacterial and viral infections for several months, that is, they protect the child from infection during that critical period when his immune system is not yet fully formed. During the first year of life, maternal antibodies disappear.
At the dawn of the development of passive immunization, serum containing antibodies (for example, horse serum) was injected directly into the recipient’s blood. Recently, a method has been developed to fractionate serum and then isolate and concentrate the required antibodies.

Immunoglobulins suitable for human use


PREPARATION	SOURCE	APPLICATION
Serum immunoglobulin		Prevents the development of measles Prevents the development of hepatitis A
Measles immunoglobulin	Mixed human plasma	Prevents the development of measles
Immunoglobulin against hepatitis B	Mixed donor plasma with high antibody titer	Used when there is a risk of infection by direct parenteral route (needle prick) or sexual contact
Anti-rabies immunoglobulin	Mixed plasma from hyperimmunized donors	Used in complex immunotherapy of rabies
Antibotulinum antitoxin	Horse specific antibodies	Treatment and prevention of botulism

5. What viruses cause acute and chronic hepatitis?


ACUTE HEPATITIS	CHRONIC HEPATITIS	PRIMARY ROUTE OF TRANSMISSION
Hepatitis A virus (HAV)	No	Fecal-oral
Hepatitis B virus (HBV)	Yes	Parenteral
Hepatitis C virus (HCV)	Yes	Parenteral
Hepatitis D virus (HDV)	Yes	Parenteral
Hepatitis E virus (HEV)	No	Fecal-oral

6. What type of immunoprophylaxis is used for hepatitis A?

A very good preventive measure is the administration of serum immunoglobulin G (IgG). If the time of possible contact with the pathogen (for example, staying in places of increased risk of infection) does not exceed 3 months, IgG is administered at a dose of 0.02 ml/kg. For longer contact, it is recommended to repeat the drug every 5 months at a dose of 0.06 ml/kg. Immunoprophylaxis with immunoglobulin G gives excellent results. However, this method is very impractical, since immunity is created only for a few months. Injection of IgG is generally safe, but fever, myalgia, and pain at injection sites may occur.

7. Is there a vaccine against hepatitis A?

There are several vaccines against hepatitis A, but only two inactivated vaccines have produced clinically acceptable results. The first study, led by Werzberger et al., demonstrated 100% effectiveness of the inactivated vaccine, which was administered once to individuals at high risk for hepatitis A infection. The study involved 1037 children aged 2 to 16 years living in northern New York, where the annual incidence of acute hepatitis A is 3%. Children were blinded and received intramuscular injections of either highly purified formalinized hepatitis A vaccine (Merck, Sharp & Dohme, West Point, PA) or placebo. In the period from 50 to 103 days after injection, 25 cases of hepatitis A were observed in the placebo group. In the group of children who received the vaccine, not a single child fell ill (p< 0,001). Таким образом, вакцина обеспечила 100 % невосприимчивость к гепатиту А. В другом исследовании, выполненном Иннис (Innis) и соавт., изучалась эффективность инактивированной вакцины (Havrix, SmitnKline, Rixensart, Belgium), отличной от той, которую использовал Верзбергер. В исследовании принимали участие более 40 000 детей из Таиланда. Сравнение эффективности вакцины с плацебо показало, что 3-кратная вакцинация (введение трех доз) предотвращает развитие гепатита А в 97 % случаев. Недавно вакцина была одобрена Food and Drug Administration (США) для назначения определенным группам населения (военным, туристам). Ее вводят внутримышечно (в дельтовидную мышцу); рекомендуемая доза - 1440 ЕД (1,0 мл); ревакцинацию проводят через 6 месяцев или 1 год.

8. How does the inactivated hepatitis A vaccine differ from the live attenuated vaccine?

Hepatitis A vaccines

	INACTIVATED (KILLED)	ATTENUATED (LIVE)
Source of receipt Method of receipt	HAV cultivation in vitro Formaldehyde inactivation	Cultivation of HAV/n vitro Numerous passages through cell culture
Immunogenicity	Contains aluminum as an adjuvant; stimulates the production of antibodies against the hepatitis A virus	No adjuvant is needed; stimulates the production of antibodies against the hepatitis A virus
Flaws	Multiple revaccinations required	Theoretically, can become virulent again and cause acute hepatitis A
Availability	Industrial production in the USA and Europe	Research continues in the USA, Asia and Europe

9. What method of immunoprophylaxis is used for hepatitis B?

Prevention of hepatitis B is carried out in two ways:
1. Active immunization. Before and after exposure to the pathogen, it is recommended to use the hepatitis B vaccine, first patented in the United States in 1981.
2. Passive immunization. Hyperimmune globulin provides temporary passive immunity and is administered to some patients after exposure to the pathogen.

Hyperimmune globulin contains high concentrations of anti-HBs. This is its main difference from conventional immunoglobulin, which is obtained from plasma with varying concentrations of anti-HBs. In the USA, the titer of HBs antibodies in hyperimmune globulin exceeds 1: 100,000 (based on radioimmunoassay results).

Immunization against hepatitis B after infection

HYPERIMMUNE GLOBULIN			VACCINE
INFECTION	DOSE	TIME	DOSE	TIME
During the perinatal period	0.5 ml intramuscularly	Within 12 hours after birth	0.5 ml at birth	Within 12 hours after birth; revaccination after 1 and 6 months
During sexual intercourse	0.6 ml/kg intramuscularly	Single administration within 14 days after sexual intercourse	The vaccine is administered simultaneously with hyperimmune globulin	Immunization should begin immediately

11. How many hepatitis B vaccines are used in the United States? What is their difference?

Three vaccines have been patented for practical use in the United States. They are comparable in immunogenicity and effectiveness, but differ in the method of preparation.
1. Heptavax-B (Merck, Sharp & Dohme) was developed in 1986. It contains the surface antigen of the hepatitis B virus, isolated from the plasma of patients with chronic hepatitis. The vaccine stimulates the production of antibodies to the determinant A HBs antigen, which effectively neutralizes various subtypes of the hepatitis B virus. Its effectiveness has been confirmed by numerous facts, but its production is very expensive, and purification and inactivation require the use of various physical and chemical methods. Taking these difficulties into account, alternative methods for producing a vaccine have been developed, the leading of which is the recombinant DNA method. 1 ml of plasma-derived vaccine contains 20 μg of HBsAg.
2. Recombivax-HB was introduced in 1989 and is manufactured by Merck, Sharp & Dohme Research Laboratories (West Point, PA). It is a non-infectious, non-glycolysed vaccine containing HBsAg subtype adw, produced using recombinant DNA technology. Yeast cells (Saccharomyces cerevisiae), in which HBsAg is fixed, cultured, centrifuged and homogenized using glass beads, after which HBsAg is purified and absorbed on aluminum hydroxide. 1 ml of vaccine contains 10 μg of HBsAg.
3. Engerix-B (SmithKline Biologicals, Rixensart, Belgium) is a non-infectious recombinant vaccine against hepatitis B. It contains the surface antigen of the hepatitis B virus, which is fixed on yeast cells that have undergone genetically engineered treatment. The cells are cultured, after which the HBsAg is purified and absorbed onto aluminum hydroxide. 1 ml of vaccine contains 20 μg of HBsAg.

12. How are adults and children immunized with the hepatitis B virus vaccine?

Recombivax-HB vaccine (Merck, Sharp & Dohme)

GROUP		INITIAL DOSE	IN 1 MONTH	AFTER 6 MONTHS
Little children	Child dose:	0.5 ml	0.5 ml	0.5 ml
(up to 1 0 years)	0.5 ml
Adults and children	Adult dose:	1.0ml	1.0 ml	1.0 ml
older	10 mcg/1.0 ml
The duration of the existence of antibodies is directly related to their maximum concentration obtained after the third dose of the vaccine. Observation of adult patients vaccinated with Heptavax-B showed that in 30-50% of recipients, antibodies completely disappeared or their level decreased significantly. Long-term studies have revealed that, despite the absence of anti-HBs in the blood serum, immunity to the hepatitis B virus in adults and children persists for at least 9 years. Some studies highlight the fact that over 9 years of follow-up, the decrease in anti-HBs levels in groups of homosexuals and Alaskan Eskimos (groups most at risk for hepatitis B infection) was 13-60%. However, although revaccination was not carried out, all immunized people retained 100% immunity to the disease. In some individuals who completely lost anti-HBs, “serological” outbreaks of infection were observed in subsequent years (the diagnosis was made when HBs antibodies were detected in the serum). There were no clinical symptoms and HBsAg was not detected, which means that such manifestations are not clinically significant, and stable immunity is formed after vaccination. Therefore, revaccination of healthy adults and children is not recommended. Patients with immunosuppressive conditions (eg, those on hemodialysis) should receive an additional dose of the vaccine when the level of anti-HBs decreases to 10 mIU/ml or lower. 14. Is the vaccine always effective? The main epitope of HBsAg is the determinant A, the production of antibodies to which is stimulated by hepatitis B vaccines. It is believed that determinant a forms a spatial link between amino acids 124 and 147. And although it is characterized by stability, sometimes there are variants that are not able to neutralize anti-HBs. Mutations of the hepatitis B virus have been reported that probably occur randomly and are not restored due to a deficiency of the internal enzyme polymerase. Significant differences between hepatitis B vaccines have been described (initially in Italy, but also in Japan and Gambia). According to Italian researchers, 40 of 1,600 immunized children developed symptoms of the disease, despite adequate antibody production in response to the HBV vaccine. The mutant virus had a substitution of amino acids: 145 in Italy, 126 in Japan and 141 in Gambia. Whether the mutant virus alters the clinical course of hepatitis remains unknown because there have been no large-scale epidemiological studies examining incidence, prevalence, and clinical correlation. 15. Can the administration of the hepatitis B vaccine be harmful to virus carriers? After administration of the vaccine, no adverse effects were observed in 16 chronic HBsAg carriers. Vaccination was carried out to eliminate carriage. However, the set goal was not achieved: none of the subjects observed the disappearance of HBsAg from the serum or the production of antibodies. This fact allows us to narrow the indications for vaccination against hepatitis B. 16. Is immunoprophylaxis of hepatitis C advisable? There are no firm recommendations for preventing the development of hepatitis C after exposure to the pathogen. The results of research on this problem remain questionable. In case of percutaneous infection, some scientists recommend prescribing immunoglobulin at a dose of 0.06 mg/kg. Moreover, prevention should begin as early as possible. However, experiments on chimpanzees have shown the insufficient effectiveness of passive immunization during infection with hepatitis C virus. Moreover, the results of recent studies indicate that neutralizing antibodies produced in humans during an infectious disease are present in the serum for only a short time and do not protect against reinfection. Thus, immunoprophylaxis of hepatitis C is a rather difficult task. It is very difficult to develop an adequate vaccine due to the presence of numerous viral genotypes, for which it is not possible to create cross-protection. 17. Is it possible to simultaneously immunize people against hepatitis A and B? At least two studies gave hepatitis A and B vaccines simultaneously to seronegative volunteers (injections in different areas of the body) and compared antibody responses in these patients with those of other subjects who received only one vaccine (either hepatitis A or hepatitis A). or against hepatitis B). No undesirable effects were noted. In contrast, one study found higher levels of antibodies to the hepatitis A virus in volunteers. Now that the hepatitis A vaccine has become available for widespread use, this early experience suggests that people can be given both vaccines at the same time without risk of developing serious side effects.

Hepatitis B virus causes serum hepatitis (viral liver disease). Its outcome is difficult to predict. In severe and weakened patients, infection occurs:

during blood transfusion,
through syringes,
sexually.

Until recently, there was no publicly available vaccine against this virus. It does not propagate in vitro in tissue culture. Reproduction occurs only in the patient's body. Therefore earlier the only way its receipt was the isolation of viral particles from the blood of sick people, and the only vaccine Antibodies isolated from the blood serum of virus carriers were used. These antibodies were used for passive immunization of patients with acute hepatitis.

The blood plasma of infected people contains varying amounts of particles of different sizes and shapes:

spherical and filamentous particles with a diameter of about 22 nm, which are devoid of DNA and are the shells of the virus;
Dane particles with a diameter of 42 nm (they are less common) are virions and consist of an envelope and a nucleocapsid with a diameter of 27 nm containing DNA molecules.

Preparations of purified nucleocapsids serve source of material to prepare a vaccine, their immunochemical properties are being intensively studied.

The hepatitis B virus belongs to the hepadnavirus family.

Its capsid is of a lipoprotein nature, which includes the surface Hbs protein and Hbs aptigen (HbsAG). The viral envelope probably consists of a lipid bilayer containing polypeptide dimers, which contain intermolecular and intramolecular disulfide bonds that determine the tertiary and quaternary structure of the protein, as well as the antigenic and immunogenic properties of HbsAG. Virions contain a nucleotide formed by the nuclear protein HbcAG. The plasma of infected people also contains another antigen - HbeAG. Viral DNA includes 3,200 nucleotides and consists of two chains:

one of which is long (L), with a fixed length,
the other is short (S), with varying length.

Transmission of the hepatitis B virus, either naturally or experimentally, occurs only in chimpanzees and humans. It cannot be propagated in tissue culture, and experiments with several types of laboratory animals have been unsuccessful.

Thus, the study of the biology of the virus was complicated by its narrow specialization. Its genome was cloned and introduced (in whole or in parts) into cell lines, after which gene expression was studied. Thus, in 1980, Dubois and his colleagues achieved success by introducing viral DNA into L-cells of mice. They found that viral DNA was integrated into cellular DNA and that HbsAG particles were secreted into the culture medium without lysis of mouse cells.

In 1981, Mariarti and his collaborators created hybrid DNA molecule, containing the DNA of the SV40 virus and a DNA fragment of the hepatitis B virus. When introduced into the kidney cells of monkeys, it caused the synthesis of HbsAG particles. Viral DNA cloning in E. coli cells and its subsequent introduction into mammalian cell lines made it possible to overcome some of the difficulties caused by the lack of an in vitro system for virus propagation.

On the other hand, the synthesis of HbsAG in prokaryotic and eukaryotic cells using cloned viral DNA would likely help produce other types of antigens, perhaps more economical and safer for vaccine production. Thus, Rutter (USA) obtained yeast cells that form glycosylated surface antigen. The Hbc protein was also obtained, isolated from viral particles and synthesized under the control of recombinant DNA in bacteria. This protein protected chimpanzees from subsequent hepatitis B virus infection.

Use of recombinant DNA technology to obtain vaccines - a step towards the development of synthetic vaccines. Several groups of researchers have synthesized immunogenic peptides that may lead to the development of a synthetic vaccine against hepatitis B. These are two cyclic peptides that were administered intraperitoneally to mice using various adjuvants. 7 - 14 days after immunization, antibodies to the surface of the hepatitis B virus were detected.

To compile the answers, regulatory documentation of the Russian Federation and international recommendations were used.

Prevention of hepatitis B is not a topic for correspondence consultation. The best solution is to contact a full-time specialist.

What documents regulate vaccination against hepatitis B in Russia?

Order of the Ministry of Health of the Russian Federation dated March 21, 2014 N 125n “On approval of the national calendar of preventive vaccinations and the calendar of preventive vaccinations for epidemic indications”

Instructions for use of specific types of hepatitis B vaccines.

How are recombinant hepatitis B vaccines made?

Recombinant vaccines registered in the Russian Federation are produced using a baker's yeast culture to which plasmids containing the surface antigen of the hepatitis B virus (HBsAg) are added. By dividing, yeast cells increase the amount of this antigen. Purified HBsAg is obtained by destroying yeast cells and separating HBsAg from yeast components by biochemical and biophysical methods.

Persons with a known severe allergy to baker's yeast should not receive vaccines produced using yeast culture.

Do hepatitis B vaccines (for example, foreign-made ones) protect against the variants of the virus circulating specifically in Russia?

Vaccines based on recombinant HBsAg protect against all (currently six are known) varieties of the hepatitis B virus, including those that are common in Russia.

How long does hepatitis B vaccination protect? Is revaccination necessary?

Studies have shown that vaccination (three doses of the vaccine) given during early childhood can provide long-term protection against carriage of the virus. Studies have also shown the effectiveness of a primary course of hepatitis B vaccination in preventing the occurrence of infection for 22 years after vaccination given in infancy (during this period, the recombinant vaccine against hepatitis B is used in the world). There is no convincing evidence to recommend the introduction of booster vaccination against hepatitis B as part of routine immunization. In the Vaccination Calendar of various countries, including the Russian Federation, there are no recommendations for routine revaccination against hepatitis B.

Why is there protection even in the absence of a protective antibody titer?

A decrease in the level of anti-HBsAg antibodies is not a suitable criterion for deciding whether revaccination is necessary. Studies have shown that immunological memory is preserved and gives an adequate response to repeated administration of the antigen. The effectiveness of protection against HBV infection declines during adolescence ( approx. - when vaccinated in infancy), but the effectiveness regarding the chronicity of this infection and the development of the disease remains high; such cases are rarely recorded.

Source – “WHO Weekly epidemiological record”, issue June 5, 2009 (84), pp. 228-230,www.who.int/wer . “Meeting of the Expert Advisory Group on Immunization Strategy Development, April 2009. Conclusions and recommendations."

Is the hepatitis B vaccine safe?

Yes, it's safe. Hepatitis B vaccine is safe when given to newborns, infants, children, adolescents, and adults. Since 1986, tens of millions of children and adults have been vaccinated around the world and in economically developed countries, which is more than a billion doses of vaccine.

Side effects after receiving the hepatitis B vaccine are rare and usually mild. In placebo-controlled studies, with the exception of local pain, myalgia and transient fever were no more common than in the placebo group (less than 10% in children and 30% in adults). Numerous long-term studies have found no evidence of serious adverse reactions. Reports of anaphylactic reactions are very rare.

Available evidence indicates that there is no causal relationship between the hepatitis B vaccine and Guillain-Barré syndrome, demyelinating disorders, multiple sclerosis, chronic fatigue syndrome, arthritis, autoimmune disorders, asthma, sudden infant death syndrome, and diabetes. International experts confirm the excellent safety profile of the hepatitis B vaccine.

Can you get infected with the hepatitis B virus from the vaccine? Is a vaccinated person contagious?

It is impossible to become infected with hepatitis B from the vaccine. The vaccine does not contain the whole hepatitis B virus, but part of its outer shell, which cannot cause hepatitis even theoretically, but can only cause the formation of an immune response to them. For the same reasons, the vaccinated person is not a source of infection; there are no contraindications to donation.

Neonatal jaundice and vaccination

Jaundice occurs in the majority (approximately 40 to 70%) of completely healthy full-term newborns and is usually the result of natural processes occurring in the body. The yellow color of the skin is given by a special substance - bilirubin. It is found in the blood of every person and is excreted by the liver. During intrauterine life, fetal bilirubin is excreted by the mother's liver. After birth, the child’s liver is not yet able to cope with the amount of bilirubin; it gradually accumulates in the blood, and usually only on the 2-3rd day this becomes noticeable by a change in the color of the child’s skin - it acquires a yellowish tint. Gradually intensifying, jaundice becomes most pronounced by 4-5 days and completely disappears by 2-3 weeks of age without any treatment (so-called physiological jaundice).

Vaccination against hepatitis B does not affect the duration and severity of jaundice in newborns and does not in any way affect liver function. Physiological jaundice of newborns is not a contraindication to immunization.

Interchangeability of recombinant vaccines

Recombinant hepatitis B vaccines available on the international and Russian markets are considered immunologically comparable and can replace each other.

Are all hepatitis B vaccines the same?

All recombinant hepatitis B vaccines are produced using yeast culture and are completely interchangeable.

The child was given the first vaccination against hepatitis B in the maternity hospital with a vaccine from one manufacturer. The second is a vaccine from another manufacturer. The 3rd vaccination is now being planned; a vaccine from a third manufacturer is available. Is it possible to get vaccinated with different vaccines?

Any recombinant hepatitis B vaccine can be used; they are interchangeable.

What vaccines against hepatitis B are registered in the Russian Federation?

Hepatitis B vaccine is available as a single vaccine or in combination with other vaccines. In Russia today, mono-vaccines and vaccines against hepatitis B together with DTP vaccines or the ADS-M vaccine, as well as a combined vaccine against hepatitis A and B, are registered.

The immune responses and safety of these combinations are comparable to those of the vaccine components administered individually.

Who is at particularly high risk for hepatitis B infection?

Sexual partners of HBsAg-positive people;

Sexually active people who are not in long-term monogamous relationships;

People who have (had) sexually transmitted diseases;

People with viral hepatitis C (the development of hepatitis B leads to worsening liver pathology);

People with chronic liver diseases;

People who have household contact with HBsAg-positive people;

Medical and social workers, especially those in contact with blood and body fluids;

Staff and residents of social organizations for people with disabilities;

People with end-stage kidney disease, including those receiving dialysis (hemodialysis, peritoneal dialysis);

People with HIV infection;

Travelers to regions with moderate or high levels of hepatitis B virus infections;

Men who have sex with men;

Injecting drug users.

The hepatitis B vaccine is contraindicated only in those who have previously had severe allergic reactions to previous doses of the hepatitis B vaccine or to components of the vaccine (such as yeast).

Not a contraindication

Neither pregnancy nor lactation is a contraindication for the use of recombinant hepatitis B vaccines. Both premature infants and HIV-positive people can be vaccinated. Vaccination against hepatitis B is not contraindicated in persons with multiple sclerosis, a history of Guillain-Barre syndrome, or autoimmune diseases (for example, systemic lupus erythematosus or rheumatoid arthritis).

Is it possible to get a free hepatitis B vaccine and for whom?

In accordance with the National Calendar of Preventive Vaccinations of the Russian Federation, all children of any age and adults under 55 years of age can be vaccinated against hepatitis B free of charge (at the expense of state funding) in local clinics.

Tell me, what determines the age limit (up to 55 years) for vaccinating adults against hepatitis B in the Russian Vaccination Calendar? Is vaccination possible at age 85?

The national vaccination calendar of the Russian Federation is also a kind of financial guarantee of the state, which indicates which vaccinations at what age can be obtained at the expense of the state. Thus, the state provides free vaccination against hepatitis B to certain groups of people. The rest are at your own expense. There are no medical age restrictions for hepatitis B vaccination.

Vaccination against hepatitis B and pregnancy planning.

I have the last third vaccine against hepatitis B left. I am planning a pregnancy, how long after vaccination can I no longer use protection?

The hepatitis B vaccine does not require any delays in the onset of pregnancy.

I received my first injection against hepatitis, but I am going to get pregnant, is it possible, since I still have to have an injection in a month and six months?

In this case, the doctor may recommend a second vaccination 4 weeks after the first vaccination, and then immediately plan a pregnancy. Two vaccinations already provide fairly high protection against hepatitis B, and during pregnancy you will undergo quite a lot of medical examinations, and after childbirth you may receive blood transfusions. Two vaccinations will greatly reduce the risk of hepatitis B infection, but one will not. The third vaccination can be done immediately after pregnancy; breastfeeding is not a contraindication.

We are planning a pregnancy, my husband was (planned to be) vaccinated against hepatitis B. Should we postpone planning?
Vaccination of the husband with any vaccines, including hepatitis B, has nothing to do with planning a pregnancy. There is no need to postpone planning because of your husband’s vaccination; the husband’s vaccination does not affect the occurrence and course of pregnancy in any way. On the contrary, a husband vaccinated against infections is part of the reliable protection of the pregnant woman and the unborn baby.

Hepatitis B vaccination and pregnancy

Ideally, a woman should be fully vaccinated by the time she becomes pregnant. Although the risk to the fetus from both inactivated and live vaccines has not been strictly proven, their use may coincide with the birth of a child with a birth defect, creating a situation that is difficult to interpret. In this regard, the question of vaccinating a pregnant woman should be raised only in special cases, for example, during an upcoming move to an endemic area or in contact with a vaccine-preventable infection to which the woman is not immune. Pregnancy is not a contraindication to hepatitis B vaccination ( .

Is it possible to get a third (last) hepatitis B vaccine during pregnancy?

Vaccines against hepatitis B are inactivated and are not contraindicated during pregnancy. But, usually, vaccination during pregnancy is carried out in case of high risk for the pregnant woman of any infections (influenza, rabies, tetanus and others at the discretion of the doctor). Thus, if there is no great threat of infection, taking into account the existing protection from two vaccinations against hepatitis B, it can be recommended to get a third vaccination after childbirth. Breastfeeding women can be vaccinated with any vaccines without restrictions.

Vaccination and breastfeeding

Breastfeeding is not a contraindication to a woman’s vaccination; hepatitis B vaccines do not pose a threat to the health of her and the child ( Guidelines MU 3.3.1.1123-02 “Monitoring of post-vaccination complications and their prevention” approved. Chief State Sanitary Doctor of the Russian Federation May 26, 2002)

Vaccination of persons with acute diseases

As in the case of vaccination against other infections, the introduction of vaccination against hepatitis B to persons during an acute illness or exacerbation of a chronic illness (with or without fever) should be postponed until recovery (relief of the exacerbation).

Vaccination of persons with chronic diseases

Vaccination is temporarily postponed until the exacerbation stops. As in the case of vaccination against other infections, the introduction of vaccination to persons during an acute illness or an exacerbation of a chronic illness (with or without fever) should be postponed until recovery (the exacerbation has stopped). Outside of an exacerbation, vaccination can be carried out against the background of the treatment received.

Vaccination of children with frequent ARVI

Is it necessary to wait for the end of catarrhal symptoms after the temperature drops?

Frequent ARVI does not indicate the presence of “secondary immunodeficiency” and cannot be a reason to avoid vaccinations. Vaccinations are carried out soon (5-10 days) after the next ARVI; residual catarrhal symptoms (runny nose, cough, etc.) are not an obstacle to vaccination. ( Guidelines MU 3.3.1.1123-02 “Monitoring of post-vaccination complications and their prevention” approved. Chief State Sanitary Doctor of the Russian Federation May 26, 2002.

Hepatitis B vaccination and various medications

The instructions for use of recombinant vaccines against hepatitis B do not indicate any medicinal substances, the use of which can serve as an exemption for vaccination.

Vaccination schedule against hepatitis B in Russia

When vaccination begins in the maternity hospital, children from risk groups are carriers of the hepatitis B virus (those born to mothers who are carriers of HBsAg; patients with viral hepatitis B or those who have had viral hepatitis B in the third trimester of pregnancy; those who do not have test results for markers of hepatitis B; drug addicts, in families , in which there is a carrier of HBsAg or a patient with acute viral hepatitis B and chronic viral hepatitis)

(scheme 0-1-2-12)

Second vaccination at 1 month

Third vaccination at 2 months

Fourth vaccination at 12 months (can be done simultaneously with measles-rubella-mumps vaccination)

When vaccination begins in the maternity hospital, children born to mothers NOT from RISK GROUPS for hepatitis B

(scheme 0-1-6 months)

– first vaccination within the first day after birth,

Second vaccination at 1 month of age

Third vaccination at 6 months (usually at the same time as the third diphtheria-tetanus-pertussis-polio vaccination)

Standard vaccination schedule for children (not vaccinated at the maternity hospital) and adults also 0-1-6 months (where 0 is the date of the first vaccination, the second vaccination is a month after the first, the third is 6 months from the first);

Standard regimen for children and adults in close contact with hepatitis B virus carriers – 0-1-2-12 months.

Simultaneous administration with other vaccines

In accordance with the recommendations of the National Calendar of Preventive Vaccinations of the Russian Federation, it is allowed to administer vaccines (except for vaccines for the prevention of tuberculosis) used within the framework of the National Calendar of Preventive Vaccinations on the same day with different syringes in different parts of the body.

International and developed country recommendations state that if the vaccines were not administered at the same time, the interval between administration of different inactivated vaccines or inactivated and live vaccines can be any ( « » ).

Thus, if the hepatitis B vaccine is not administered simultaneously with other vaccines, then it (as an inactivated vaccine) can be administered any day after the previous vaccination, even the next day.

This is what they do in maternity hospitals, where the interval between the administration of the hepatitis B vaccine (at birth) and the BCG vaccine is only a few days.

I’ve heard that it’s better not to get other vaccinations between hepatitis vaccinations, is that true?

The information that it is not advisable to take other vaccinations between hepatitis vaccinations is some kind of myth; such restrictions do not exist. For example, in the National Calendar of Preventive Vaccinations of the Russian Federation, between the second and third vaccination against hepatitis B, children are regulated by the administration of a vaccine against diphtheria-tetanus-whooping cough-poliomyelitis, pneumococcal and Hib infection.

Simultaneous vaccination against hepatitis A and B

What time interval should be between vaccination against hepatitis A and hepatitis B? I heard that you cannot vaccinate against hepatitis A and B at the same time.

In accordance with the recommendations of the National Calendar of Preventive Vaccinations of the Russian Federation, it is allowed to administer vaccines (except for vaccines for the prevention of tuberculosis) on the same day with different syringes to different parts of the body. A combined vaccine against hepatitis A and B in one foreign-made syringe has also been registered in Russia and around the world.

The instructions for use of the hepatitis B vaccine state that the hepatitis B vaccine is administered to children and adults in the deltoid muscle of the shoulder, and for infants - in the thigh. In our clinic, all children receive this vaccine in the buttock, adults sometimes under the shoulder blade. Is this correct?

Wrong. In accordance with the law, medications must be administered only in the manner indicated in the instructions for their use. Instructions for hepatitis B vaccines indicate intramuscular administration in older children and adults in the deltoid muscle (shoulder), and in young children in the thigh. The instructions for use of some hepatitis B vaccines state that they should not be injected into the buttock.

According to international recommendations ( WHO position on hepatitis B vaccines, 2009, hepatitis B vaccine should be given intramuscularly into the anterolateral thigh (infants and children under 2 years of age) or into the deltoid muscle (older children and adults). Administration into the buttock is not recommended, as this route of administration has been associated with reduced levels of protective antibodies (the vaccine may not penetrate the muscle due to the thickness of the subcutaneous fat) and damage to the sciatic nerve.

Therefore, for optimal development of immune protection, hepatitis B vaccines should be administered intramuscularly rather than subcutaneously (on the buttock or under the shoulder blade). As recommended by developed countries, hepatitis B vaccine administered into the buttock should not be counted as the correct dose and should be administered correctly as soon as possible after the mistaken administration ( "General Recommendations on Immunization - Recommendations of the Advisory Committee on Immunization Practices (ACIP)").

Vaccination against hepatitis B in children and adults in violation of the standard administration schedule

What official documents of the Russian Federation (orders, guidelines) determine the procedure for vaccination against hepatitis B in case of violation of the start date of administration or continuation of the vaccination course?

“The first, second and third vaccinations are carried out according to the 0-1-6 scheme (1 dose - at the start of vaccination, 2 dose - a month after 1 vaccination, 3 dose - 6 months after the start of vaccination), with the exception of children belonging to risk groups whose vaccination against viral hepatitis B is carried out according to the 0-1-2-12 scheme (1 dose - at the start of vaccination, 2 dose - a month after 1 vaccination, 2 dose - 2 months after the start of vaccination, 3 dose - 12 months from the start of vaccination).... If the timing of vaccination changes, it is carried out according to the schedules provided for in the national calendar of preventive vaccinations and in accordance with the instructions for the use of immunobiological drugs for the immunoprophylaxis of infectious diseases..."

If a child has not been vaccinated against hepatitis B in the maternity hospital, according to what schedule should he be vaccinated?

If the child has not been vaccinated against HBV in the maternity hospital, then vaccination should begin as early as possible, while maintaining the 0-1-6 month schedule;

If a child has been vaccinated against hepatitis B for more than 3 months since the first vaccination in the maternity hospital, according to what schedule should he be vaccinated next?

International recommendations and recommendations from developed countries indicate that there is no need to start vaccination again ( WHO position on hepatitis B vaccines, 2009,www.who.int/immunization/Hepatitis_B_revised_Russian_Nov_09.pdf ) – “..Data on the immunogenicity of the vaccine give reason to believe that in any age group, a break in the vaccination regimen does not require the resumption of the entire course of vaccinations. If the primary course is interrupted after the first dose, the second dose should be administered as soon as possible."

The child was vaccinated against hepatitis B before kindergarten. We managed to get 2 vaccinations; between the 2nd and 3rd vaccinations there is an interval of 1.5 years. The kindergarten nurse says we need to start vaccinating again.

According to international recommendations, with such increases in the intervals between vaccinations against hepatitis B, no additional vaccinations are required; a third vaccination against hepatitis B is simply carried out in the near future, providing long-term immunity for several decades.

I tried to complete the hepatitis B vaccination cycle twice, but I don't remember exactly whether I completed it (a series of three shots). Now I don’t know what to do. Will it be safe to start the entire vaccination cycle all over again, despite, say, 3 uncompleted cycles earlier?

What is the maximum interval between the first and third hepatitis B vaccine? Is it possible to get subsequent vaccinations with vaccines from other manufacturers?

Theoretically, the maximum interval between the start and end of the course of vaccination against hepatitis B can be any. But delaying the second and third vaccinations delays the formation of stable long-term immunity.

There is no difference in immunogenicity, even if subsequent vaccinations are carried out with vaccines from other manufacturers, recombinant hepatitis B vaccines are interchangeable.

What happens if you don't get the second and third or third dose of hepatitis B vaccine at all?

What time interval is allowed between the second and third vaccination against hepatitis B? Are two vaccinations enough to obtain lasting immunity against hepatitis B?

The minimum interval between the second and third vaccination should be at least 4 weeks. The maximum interval is not regulated. To form stable long-term immunity, a completed vaccination course of three vaccinations is required.

Two vaccinations provide a protective level of immunity for most vaccinated people, but how long it will last and how guaranteed it is is unknown.

Can hepatitis B vaccinations be administered earlier than the standard age or due date?

The first vaccination against hepatitis B was given to the child at birth, and a second was given a month later. At the age of 5 months, they received the third vaccination against hepatitis B. Is this correct, since the vaccination calendar indicates that the third vaccination against hepatitis B is carried out at 6 months?

This is wrong. Lower levels of immune response are observed in infants who complete the standard series of vaccinations earlier than 6 months of age. In this case, the third vaccination is not taken into account. The third vaccination should be repeated when the child is 6 months old (not earlier than 24 weeks).

The child is 3 months old. At the clinic, they give 3 vaccinations at once in one day (DTP, against polio and hepatitis B). Can they be done all at once or is it better to split them up over a few days? Is it worth getting all three vaccinations, or is it better to temporarily skip the hepatitis B vaccine and get the rest?

The simultaneous administration of vaccines is an international standard used to ensure the safety of the child. Simultaneous administration reduces the psychological burden on the child and parents, reduces the risk of adverse reactions, and reduces the number of visits to a medical facility (and, accordingly, the risk of contact there with patients with acute respiratory infections). Stretching out vaccination by introducing vaccinations one at a time only leads to the fact that the child is constantly being taken for injections, with each injection there is a possibility of developing side effects, and with each visit to the clinic there is a risk of contracting another ARVI. Separate immunization does not bring any benefit; this is a Russian delusion and harms the child.

When three vaccines are given to an infant at the same time, one shot may be given in the left thigh, another shot in the right thigh, and a third shot in the deltoid muscle. Or, if possible, use modern multicomponent vaccines, which will reduce the number of injections.

Refusal to vaccinate will leave the child unprotected from a dangerous infection. Studies show that if a child has not been vaccinated against hepatitis B at the required age along with all other vaccinations, then parents generally forget to administer this vaccination and do not bring the child to a medical facility for this.

The child is 1 year and 2 months old. He started getting vaccinated against hepatitis B at 3 months; today, 4 months have passed since the second vaccination. Now the pediatrician insists on a third vaccination against hepatitis B and suggests combining it with vaccination against measles, rubella and mumps. Can all this be done in one day, or broken up separately? Or does hepatitis B vaccination need to be started again?

It is necessary to do these vaccinations at the same time in order to reduce the psychological and injection burden on the child and not take him for an injection every month. Simultaneous administration of vaccines is the global standard and the standard in developed countries. There is no need to restart hepatitis B vaccination. Just give the third shot.

Due to the lack of vaccine in the clinic, the child has not yet received the third DTP vaccination until now. Is it possible to get a third hepatitis B vaccine now without getting a third DPT vaccine?

Vaccinations can be done either on the same day or separately. The absence of another DTP does not in any way entail a ban on vaccinations against hepatitis B. This is some kind of myth.

Is it possible for a child to be vaccinated with BCG and hepatitis B on the same day?

In the Order of the Ministry of Health of the Russian Federation dated March 21, 2003 N 109 “On improving anti-tuberculosis measures in the Russian Federation”, Appendix N 5 states - “Instructions for vaccination and revaccination against tuberculosis with BCG and BCG-M vaccines. - “...On the day of vaccination to avoid contamination, no other parenteral manipulations are performed on the child, including examination of the child for phenylketonuria and congenital hypothyroidism.”

The simultaneous administration of vaccines does not directly affect the development of immunity; such separation is carried out for safety reasons regarding the BCG vaccine.

Vaccination of children and adults who are in close contact with carriers of the hepatitis B virus is carried out according to the scheme 0-1-2-12 months.

When vaccination begins in the maternity hospital, children born to mothers who are carriers of the hepatitis B virus (scheme 0-1-2-12).

Children born weighing less than 1500 g to HbsAg carrier mothers are vaccinated against hepatitis B in the first 12 hours of life. Considering the possibility of their insufficient immune response, simultaneous administration of human immunoglobulin against hepatitis B in a dose of 100 IU is recommended for such children.

I am a carrier of HBsAg antigen. My daughter is 17 months old. Vaccination against hepatitis B is done according to the 0-1-2 scheme. No vaccinations were given at 12 months. Should you get the vaccine now? Or get tested for the amount of antibodies to the virus, and if it is normal, then you don’t have to do it?

Your daughter’s primary emergency vaccination regimen has not been completed. It must be completed; the examination does not make sense, since it cannot say how stable the immunity is if the course of vaccination is not completed. You just need to get the fourth vaccination. Otherwise, long-term protective immunity will not be formed.

The child has previously been vaccinated against hepatitis B with three vaccinations. The child's father was recently diagnosed with chronic hepatitis B, the mother is healthy, vaccinated 2 years ago. Do the baby and mother need additional vaccinations?

My boyfriend is a carrier of the hepatitis B virus. We found out by chance. Tests showed that I am not infected. How to get vaccinated? Will the vaccine harm me if I am also already infected?

In this case, vaccination against hepatitis B is urgently indicated. For persons who are in close contact with carriers of the hepatitis B virus, vaccination is recommended according to the emergency schedule of 0-1-2-12 months, where 0 is the date of the first vaccination. Until you have received at least three vaccinations, it is recommended to protect yourself using a condom.

If you are already infected, the vaccine will not cause harm, only benefit.

I have chronic hepatitis C. Is there any peculiarity in vaccinating a child of such a mother?

If you do not have the hepatitis B virus, then the child is vaccinated as usual, in accordance with the National Calendar, according to a schedule of three vaccinations.

It is strongly recommended for those infected with the hepatitis C virus to be vaccinated against hepatitis B, since the addition of the hepatitis B virus to the existing infection leads to serious liver pathology.

Vaccination of children and adults with various health conditions

The child was born at 37 weeks, low weight, the effects of hypoxia are still present, decreased muscle tone, decreased hemoglobin level. Is it possible to vaccinate against hepatitis B against this background?

Immunization against hepatitis B in premature infants is carried out throughout the world and is not contraindicated for them either at birth or after.

During pregnancy, the child was diagnosed with a liver cyst, in the maternity hospital there was a medical exemption from vaccinations, bilirubin was high, and jaundice lasted up to 4 months. Will this cause any complications with the liver?

The vaccine against hepatitis B does not contain the whole virus, either live or in inactivated form, only a fragment of its shell, it is not capable of causing liver disease, on the contrary, it protects against the development of liver disease - chronic hepatitis B and its consequences (cirrhosis, cancer).

Children in the first months of life who have suffered serious illnesses (sepsis, hemolytic anemia, pneumonia, hyaline membrane disease, etc.) and recovered from them are vaccinated in the usual manner.

At three months the child was not vaccinated against hepatitis B because he had low hemoglobin. When is the best time to get the third vaccination? The doctor said - only if there is a normal blood test.

Anemia detected during examination cannot in any way be a medical reason for vaccination. Moreover, a repeated blood test cannot be a factor in admission to vaccination - treatment and prevention of anemia in a child should proceed on its own, without any connection to vaccinations.

Therefore, the second hepatitis B vaccine should be given as soon as possible.

For chronic diseases that are not characterized by exacerbations (anemia, malnutrition, rickets, asthenia, etc.), the child should be vaccinated and then treatment should be prescribed or continued. Unfortunately, in Russian conditions such patients are often “prepared” for vaccination, which only delays its implementation. Prescription of general tonics, stimulants, vitamins, adaptogens, etc. cannot be a reason to delay vaccination. ( Guidelines MU 3.3.1.1095-02 "Medical contraindications for preventive vaccinations with drugs from the national vaccination calendar."

Vaccination against hepatitis B is carried out immediately after the birth of a child, since he is vulnerable and does not have protective immunity; the virus is easily transmitted during medical procedures and in everyday life.
Hepatitis B infection in infancy leads to liver cancer and death by the age of 17 in some children.

Russia is a medium-endemic territory in terms of HBsAg prevalence in the population - from 2 to 7%. Therefore, universal vaccination of newborns against hepatitis B has been introduced into the Russian vaccination calendar. Delaying vaccinations leads to delaying protection against hepatitis B. As practice shows, if vaccination against hepatitis B is not done immediately, a considerable part of parents then do not vaccinate their child against hepatitis B at all, since this requires scheduling a separate visit to the doctor, and parents say that don't have time for this.

There are no carriers of the hepatitis B virus in our family, why vaccinate a child in the maternity hospital?

In the first months of life, a child is subjected to many medical procedures during examinations and examinations. Medical procedures throughout the world pose a risk of transmission of the hepatitis B virus. To become infected with the hepatitis B virus, minimal, invisible amounts of infected material (blood and other body fluids) are sufficient. The hepatitis B virus is 100 times more contagious than HIV.

In maternity hospitals, when the child is vaccinated for the first time, the mother is asked to sign a consent form. How competently can a mother assess her child’s readiness for vaccination?

There are very few contraindications for vaccinating a baby in the maternity hospital; they are associated with his very serious condition (some kind of serious illness visible to everyone at the time of newborn). The presence or absence of a serious illness can be assessed by anyone, not just a medical professional. You can familiarize yourself with the guidelines MU 3.3.1.1095-02 “Medical contraindications for preventive vaccinations with drugs from the national vaccination calendar.”

Will a person vaccinated against hepatitis B test positive for HBsAg? Or should the vaccine not give a positive result?

Vaccination against hepatitis B forms protective antibodies to this virus, which in a blood test are called anti-HBsAg or a-HBsAg, but cannot in any way cause the presence of HBsAg (HBs antigen) in the blood. HBsAg itself (HBs antigen, surface antigen of the hepatitis B virus) can also be detected in a vaccinated person if infection with it occurred before the formation of protective immunity or HBsAg was already present before vaccination, but was not detected.

Hepatitis B is an acute or chronic liver disease caused by the DNA-containing hepatitis B virus (HBV). Transmission of infection occurs parenterally. Hepatitis B has various clinical and morphological variants: from “healthy* carriage to malignant forms, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma EPIDEMIOLOGY

Hepatitis B is an anthroponotic infection: the only source of infection is humans. The main reservoir is “healthy” virus carriers; Patients with acute and chronic forms of the disease are of less importance.

Currently, according to incomplete data, there are about 300 million virus carriers in the world, including more than 5 million living in our country.

HBV is transmitted exclusively by the parenteral route: through the transfusion of infected blood or its preparations (plasma, red blood cells, human albumin, protein, cryoprecipitate*, antithrombin III, etc.), the use of poorly sterilized syringes, needles, cutting instruments, as well as scarification, tattoos , surgical interventions, dental treatment, endoscopic examination, duodenal intubation and other manipulations during which the integrity of the skin and mucous membranes is disrupted.

Natural modes of transmission of HBV include transmission through sexual contact and vertical transmission from mother to child. Sexual transmission should also be considered parenteral, since infection occurs through inoculation of the virus through microtraumas of the mucous membranes of the genital organs.

Infection of children from mothers who are HBV carriers occurs mainly during childbirth as a result of contamination from blood-containing amniotic fluid through macerated skin and mucous membranes of the child. In rare cases, a child becomes infected immediately after birth through close contact with an infected mother. Transmission of the infection in these cases occurs through microtrauma, i.e., parenterally, and possibly through breastfeeding. Infection of the child occurs, most likely, not through milk, but as a result of the contact of the mother’s blood (from cracked nipples) on the macerated mucous membranes of the child’s oral cavity.

The population's susceptibility to the hepatitis B virus appears to be widespread, and a person's encounter with the virus usually results in asymptomatic infection. The frequency of atypical forms cannot be accurately counted, but judging by the identification of seropositive individuals, then for each case of manifest hepatitis B there are tens and even hundreds of subclinical forms.

As a result of hepatitis B, persistent lifelong immunity is formed. Recurrence of the disease is unlikely.

PREVENTION

It consists, first of all, of a thorough examination of all categories of donors with a mandatory blood test for HBsAg at each donation using highly sensitive methods of its identification (ELISA, RIA), as well as determination of ALT activity.

Persons who have had viral hepatitis in the past, patients with chronic liver diseases, as well as persons who have received transfusions of blood and its components over the past 6 months are not allowed to donate. It is prohibited to use blood and its components from donors who have not been tested for HB^Ag for transfusion.

To improve the safety of blood products, it is recommended to screen donors not only for HBsAg, but also for anti-HBc. Removal from donation of persons with anti-HBc, considered as hidden carriers of HBsAg, practically eliminates the possibility of post-transfusion hepatitis B.

To prevent infection of newborns, all pregnant women are tested twice for HBjAg using highly sensitive methods: when registering a pregnant woman (8 weeks of pregnancy) and when registering for maternity leave (32 weeks). If HBsAg is detected, the question of pregnancy should be decided strictly individually. It is important to consider that the risk of intrauterine infection of the fetus is especially high if a woman has HBjAg and is negligible if it is absent, even if HBjAg is detected in high concentrations. The risk of infection of the child during delivery by cesarean section is also significantly reduced.

Interruption of infection transmission routes is achieved by using disposable syringes, needles, scarifiers, probes, catheters, blood transfusion systems, other medical instruments and equipment used during manipulations associated with violating the integrity of the skin and mucous membranes.

All medical instruments and reusable equipment must undergo thorough pre-sterilization cleaning and sterilization after each use.

For the prevention of post-transfusion hepatitis, strict adherence to the indications for hemotherapy is of great importance. Transfusion of canned blood and its components (erythrocyte mass, plasma, antithrombin III, factor VII concentrates) is done only for health reasons and noted in the medical history. It is necessary to switch, if possible, to transfusion of blood substitutes or, as a last resort, transfusion of its components (albumin*, specially washed red blood cells, protein, plasma). This is due to the fact that pasteurization of plasma (60 °C, 10 hours), although it does not guarantee complete inactivation of HBV, still reduces the risk of infection; The risk of infection during transfusion of albumin*, protein is even lower, and the risk of infection during transfusion of immunoglobulins is negligible.

In departments at high risk of hepatitis B infection (hemodialysis centers, intensive care units, intensive care wards, burn centers, oncology hospitals, hematology departments, etc.), hepatitis B prevention is achieved through strict adherence to anti-epidemic measures: the use of disposable instruments, assigning each device to a fixed group of patients, thorough cleaning of blood from complex medical devices, maximum separation of patients, limitation of parenteral interventions, etc. In all these cases, HBsAg identification is carried out using highly sensitive methods and at least once a month.

To prevent occupational infections, all employees must work with blood wearing rubber gloves and strictly observe personal hygiene rules.

To prevent the spread of infection in families of patients with hepatitis and HBV carriers, routine disinfection is carried out, personal hygiene items (toothbrushes, towels, bed linen, washcloths, combs, shaving accessories, etc.) are strictly individualized. All family members are explained under what conditions infection can occur. Family members of patients with chronic hepatitis B and carriers of HBgAg are under medical supervision.

Specific prevention of hepatitis B is achieved through passive and active immunization of children at high risk of infection.

For passive immunization, immunoglobulin with a high content of antibodies to HBsAg is used (titer in the passive hemagglutination reaction is 1:100,000-1:200,000). This immunoglobulin is obtained from the plasma of donors in whose blood anti-NV is detected. in high titer.

Indications for immunoglobulin prophylaxis in children.

Children born to mothers who are carriers of HBaAg or who become ill with acute hepatitis B in the last months of pregnancy (immunoglobulin is administered immediately after birth, and then again after 1, 3 and 6 months).

After virus-containing material enters the body (blood or its components are transfused from a patient or a carrier of HBV, accidental cuts, injections with suspected contamination of clothing with virus-containing material). In these cases, immunoglobulin is administered in the first hours after the suspected infection and after 1 month.

If there is a long-term threat of infection (children admitted to hemodialysis centers, patients with hemoblastosis, etc.), it is re-administered at various intervals (every 1-3 months or every 4-6 months). The effectiveness of passive immunization depends primarily on the timing of immunoglobulin administration. When administered immediately after infection, the preventive effect reaches 90%, in up to 2 days - 50-70%. and when administered after 5 days, immunoglobulin prophylaxis is practically ineffective.

With intramuscular injection of immunoglobulin, the peak concentration of anti-HB in the blood occurs after 2-5 days. To obtain a faster protective effect, immunoglobulin can be administered intravenously.

The period of immunoglobulin elimination ranges from 2 to 6 months. A reliable protective effect is noted only in the first month after administration, therefore, to obtain a prolonged effect, repeated administration of immunoglobulin is necessary. In addition, the use of immunoglobulin is effective only at a low infectious dose of HBV. In case of massive infection (blood transfusion, plasma, etc.), immunoglobulin prophylaxis is ineffective.

Despite the shortcomings, the introduction of specific immunoglobulin can take its rightful place in the prevention of hepatitis B. According to the literature, its

Temporary administration of specific immunoglobulin can prevent hepatitis B infection in 70-90% of vaccinated people.

For active prevention of hepatitis B, genetically engineered vaccines are used.

In our country, several recombinant vaccines against hepatitis B have been created (produced by Combiotech JSC, etc.). In addition, several foreign drugs have been registered and approved for use (Engerix B*; HB-VAX II*, Euvax B*; Shenvak-B*; Eberbiovak AB*, Regevak B*, etc.).

The following are subject to active immunization against hepatitis B:

♦ all newborns in the first 24 hours of life, including children born to healthy mothers and children at risk, which include newborns born to mothers who are carriers of HBsAg, have viral hepatitis B, or have had viral hepatitis B in the third trimester of pregnancy, with no results examinations for markers of hepatitis B, as well as those classified as risk groups: drug addicts, in families in which there is a carrier of HBsAg or a patient with acute viral hepatitis B and chronic viral hepatitis;

♦ newborns in areas where hepatitis B is endemic, with a HBsAg carriage level of more than 5%;

♦ patients who often undergo various parenteral procedures (chronic renal failure, diabetes, blood diseases, proposed surgery using a heart-lung machine, etc.);

> persons in close contact with HBgAg carriers (in families, closed children's groups);

♦ medical personnel of hepatitis departments, hemodialysis centers, blood service departments, surgeons, dentists, pathologists;

♦ persons who were accidentally injured by instruments contaminated with the blood of patients with hepatitis B or carriers of HB£Ag.

Vaccination is carried out three times according to the schedule of 0, 1, 6 months, for healthy children - 0, 3, 6 months. Other schemes are also acceptable: 0.1, 3 months or 0.1, 12 months. Revaccination is carried out every 5 years.

Only persons who do not have HBV markers detected in their blood (HB^g, anti-HBc, anti-HB5) are subject to active immunization. If one of the hepatitis B markers is present, vaccination is not carried out.

The effectiveness of vaccination is very high. Numerous studies show that when the vaccine is administered according to a 0, 1, 6 month regimen, 95% of individuals develop protective immunity, providing reliable protection against HBV infection for 5 years or more.

There are no contraindications to vaccination against hepatitis B. The vaccine is safe and areactogenic. Vaccination can reduce the incidence of hepatitis B by 10-30 times.

To prevent vertical transmission of HBV, the first phase of vaccination is carried out immediately after birth (no later than 24 hours), then vaccinated after 1, 2 and 12 months. For this purpose, combined passive-active immunization of newborns from mothers with hepatitis B or virus carriers can be used. Specific immunoglobulin is administered immediately after birth, and vaccination is carried out in the first 2 days. Vaccination is carried out in a regimen of 0.1, 2 months with revaccination at 12 months. This passive-active immunization reduces the risk of infection of the child in mothers with HBEAg from 90 to 5%.

Widespread implementation of vaccination against hepatitis B will reduce the incidence of not only acute but also chronic hepatitis B, as well as cirrhosis and primary liver cancer.

CLASSIFICATION

Clinically, hepatitis B, like hepatitis A, is classified according to type, severity and course. The criteria for determining the type and distinguishing clinical forms are the same as for hepatitis A. However, along with mild, moderate and severe forms, there is also a malignant form, which is observed almost exclusively with hepatitis B and hepatitis delta, and the course, in addition to acute and protracted, can be chronic.

Clinical and laboratory criteria for anicteric, erased, subclinical, as well as mild, moderate and severe forms of hepatitis B are not fundamentally different from those for hepatitis A.

ETIOLOGY

The causative agent is a DNA-containing virus from the hepadnavirus family (from the Greek hepar - liver and English DNA - DNA).

Hepatitis B virus (Dane particles) is a spherical formation with a diameter of 42 nm, consisting of an electron-dense core (nucleocapsid) with a diameter of 27 nm and an outer shell with a thickness of 7-8 nm. In the center of the nucleocapsid there is a gene virugia, represented by double-stranded DNA.

The virus contains 3 antigens that are essential for laboratory diagnosis of the disease:

♦ HB^g - nuclear, core antigen, having a protein nature;

♦ HB^Ag - transformed HB^g (infectiousness antigen);

♦ HBsAg - surface (Australian antigen), forming the outer shell of the Dane particle.

HBV is highly resistant to high and low temperatures. At a temperature of 100 °C, the virus dies in 2-10 minutes; at room temperature it persists for 3-6 months, in the refrigerator - 6-12 months, frozen - up to 20 years; in dried plasma - 25 years. The virus is extremely resistant to exposure chemical factors: a 1-2% solution of chloramine kills the virus after 2 hours, a 1.5% solution of formalin - after 7 days. The virus is resistant to lyophilization, ultraviolet rays, acids, etc. When autoclaving (120 ° C), activity. The virus is completely suppressed only after 5 minutes, and when exposed to dry heat (160 ° C) - after 2 hours.

PATHOGENESIS

In the mechanism of development of the pathological process in hepatitis B, several leading links can be distinguished:

♦ introduction of the pathogen - infection;

♦ fixation on the hepatocyte and penetration into the cell;

<>reproduction and release of the virus onto the surface of the hepatocyte. and also in

blood; o - inclusion of immune reactions aimed at eliminating the pathogen;

♦ damage to extrahepatic organs and systems;

■«■ formation of immunity, release from the pathogen, recovery.

CLINICAL PICTURE

In typical cases of the disease, four periods are distinguished: incubation, initial (pre-icteric), peak period (icteric) and convalescence.

The incubation period lasts 60-180 days, usually 2-4 months, in rare cases it is shortened to 30-45 days or extended to 225 days. The duration of the incubation period depends on the infecting dose and the age of the children. With massive infection (blood or plasma transfusions), the incubation period is short - 1.5-2 months, and with parenteral manipulations (subcutaneous and intramuscular injections) and especially with domestic infection, the incubation period is 4-6 months. In children in the first months of life, the incubation period is usually shorter (92.8±1.6 days) than in children of older age groups (117.8±2.6 days).

Clinical manifestations of the disease in this period are completely absent, but, as with hepatitis A, at the end of incubation in the blood there is a constantly high activity of hepatocellular enzymes and the identification of markers of an actively ongoing infection: HBjAg, HBjAg, anti-HBc IgM.

Initial (orangetush) period. The disease most often (65%) begins gradually. An increase in body temperature is not always noted (40%) and usually not on the first day of illness. The patient may experience lethargy, weakness, increased fatigue, and decreased appetite. Often these symptoms are so mild that they are overlooked, and the disease begins with darkening of the urine and the appearance of discolored feces. In rare cases, the initial symptoms are pronounced: nausea, repeated vomiting, dizziness, drowsiness. Dyspeptic disorders often occur: loss of appetite up to anorexia, aversion to food, nausea, vomiting, flatulence, constipation, and less commonly, diarrhea. Older children complain of dull pain in the abdomen. When examined during this period, general asthenia, anorexia, enlargement, hardening and tenderness of the liver, as well as darkening of urine and often discoloration of feces can be detected.

Muscular and joint pain, often found in adult patients, is very rare in children in the pre-icteric period.

Rarely in the pre-icteric period, skin rashes, flatulence, and stool disorders are observed.

Catarrhal phenomena are not at all characteristic of hepatitis B.

The most objective symptoms in the initial period are enlargement, hardening and tenderness of the liver.

Changes in peripheral blood in the initial period of hepatitis B are not typical. Only slight leukocytosis and a tendency to lymphocytosis can be noted; ESR is always within normal limits.

In all patients, already in the preicteric period, high activity of ALT, AST and other hepatocellular enzymes is detected in the blood serum; at the end of this period, the content of conjugated bilirubin in the blood increases, but the indicators of sediment samples, as a rule, do not change, and there is no dysproteinemia. HB5Ag, HBpAg, and anti-HBc IgM circulate in the blood in high concentrations, and viral DNA is often detected.

The duration of the initial (pre-icteric) period can range from several hours to 2-3 weeks; on average 5 days.

Jaundice period (the height of the disease). 1-2 days before the onset of jaundice, patients notice darkening of the urine and, in most cases, discoloration of the stool. Unlike hepatitis A, with hepatitis B, the transition of the disease into the third, icteric period, in most cases is not accompanied by an improvement in the general condition. On the contrary, in many children the symptoms of intoxication intensify.

Jaundice increases gradually, usually over 5-7 days, sometimes 2 weeks or longer. Yellowness can vary from faint yellow, canary or lemon to greenish yellow or ocher yellow, saffron. The severity and shade of jaundice are associated with the severity of the disease and the development of cholestasis syndrome.

Having reached the peak of severity, jaundice with hepatitis B usually stabilizes within 5-10 days, and only after that does it begin to decrease.

A rare symptom of hepatitis B in children is a skin rash. The rash is located symmetrically on the limbs, buttocks and torso, and is maculopapular, red, and up to 2 mm in diameter. When squeezed, the rash takes on an ocher color; after a few days, slight peeling appears in the center of the papules. These rashes should be interpreted as Gianotti-Crosti syndrome, described by Italian authors for hepatitis B.

In severe forms, at the height of the disease, manifestations of hemorrhagic syndrome are possible: pinpoint or more significant hemorrhages in the skin.

In parallel with the increase in jaundice with hepatitis B, the liver enlarges, its edge thickens, and pain occurs on palpation.

An enlarged spleen is observed less frequently than an enlarged liver. The spleen is often enlarged in more severe cases and with a long course of the disease. Enlargement of the spleen is noted throughout the acute period with a slow reverse trend. Often the spleen is palpated after the disappearance of other symptoms (with the exception of liver enlargement), which, as a rule, indicates a protracted or chronic course of the disease.

In the peripheral blood at the height of jaundice, the number of red blood cells tends to decrease. In severe forms, anemia develops. In rare cases, more severe changes in the bone marrow are possible, up to the development of panmyelophthisis.

During the icteric period, the number of leukocytes is normal or reduced. In the leukocyte formula at the height of toxicosis, a tendency towards neutrophilosis is revealed, and during the recovery period - clymphocytosis. ESR is usually within normal limits. A low ESR (1-2 mm/h) with severe intoxication in a patient with a severe form of hepatitis B is an unfavorable sign.

Convalescent, recovery period. The total duration of the icteric period with hepatitis B ranges from 7-10 days to 1.5-2 months. With the disappearance of jaundice, children no longer complain, they are active, their appetite is restored, but in half of the patients hepatomegaly remains, and in 2D there is slight hyperenzymemia. The thymol test may be elevated, dysproteinemia, etc. may occur.

In the convalescent period, HBsAg and especially HBeAg are usually no longer detected in the blood serum. but anti-HBE and anti-HBj are always detected. IgG and often anti-HB3.

The malignant form occurs almost exclusively in children of the 1st year of life. Clinical manifestations of malignant forms depend on the prevalence of liver necrosis, the rate of their development, and the stage of the pathological process. There is an initial period of the disease, or a period of precursors, a period of development of massive liver necrosis, which usually corresponds to a state of precoma and rapidly progressive decompensation of hepatic functions, clinically manifested by coma I and coma P.

The disease often begins acutely: body temperature rises to 38-39 ° C, lethargy, adynamia, and sometimes drowsiness appear, followed by attacks of anxiety or motor agitation. Dyspeptic disorders are expressed: nausea, regurgitation, vomiting (often repeated), sometimes diarrhea.

With the appearance of jaundice, the most constant symptoms are: psychomotor agitation, repeated vomiting with blood, tachycardia, rapid toxic breathing, bloating, severe hemorrhagic syndrome, increased body temperature and decreased diuresis. Vomiting “coffee grounds”, sleep inversion, convulsive syndrome, hyperthermia, tachycardia, rapid toxic breathing, hepatic breath, liver shrinkage are observed only in malignant forms of the disease. Following these symptoms or simultaneously with them, a blackout occurs with the clinical symptoms of hepatic coma.

Among the biochemical indicators, the most informative are;

o bilirubinprotein dissociation - with a high content of bilirubin in the blood serum, the level of protein complexes decreases sharply;

♦ bilirubin enzyme dissociation - with a high bilirubin content, a decrease in the activity of liver cell enzymes is observed, as well as a decrease in the level of blood clotting factors.

The general principles of treatment for patients with acute hepatitis B are the same as for hepatitis A. However, it must be taken into account that hepatitis B, unlike hepatitis A, often occurs in a severe and malignant form. In addition, the disease can result in the formation of chronic hepatitis and even cirrhosis.

Currently, there is no fundamental objection to children with mild and moderate forms of hepatitis B being treated at home. The results of treating such patients at home are no worse, and in some respects even better, than in a hospital.

Specific recommendations regarding physical activity, therapeutic nutrition and criteria for their expansion are basically the same. as with hepatitis A; one should only take into account that the duration of all restrictions for hepatitis B is usually somewhat longer, in full accordance with the course of the disease.

In general, we can say that with a smooth course of the disease, all restrictions on movement and nutrition should be lifted after 6 months from the onset of the disease, and sports can be allowed after 12 months.

Drug therapy is carried out according to the same principles as for hepatitis A. In addition to this basic therapy, for moderate and severe forms of hepatitis B, interferon can be used intramuscularly at a dose of 1 million units 1-2 times a day for 15 days.

In order to prevent the transition of an acute process to a chronic one, it is advisable to prescribe an interferon inducer - cycloferon* (at the rate of 10-15 mg/kg), the course duration is 15 doses.

In severe forms of the disease, for the purpose of detoxification, intravenous administration of a 1.5% solution of reamberin*, rheopolyglucin\ 10% glucose solution* up to 500-800 ml/day is indicated, and glucocorticoids are also prescribed at the rate of 2-3 mg/kg per day for prednisolone in during the first 3-4 days (until clinical improvement) followed by a rapid reduction in dose (course no more than 7-10 days). In children 1 year of age, moderate forms of the disease are also indications for prescribing glucocorticoids.

If a malignant form is suspected or there is a threat of its development, the following is prescribed:

* glucocorticoids up to 10-15 mg/kg per day with prednisolone intravenously in equal doses every 3-4 hours without an overnight break;

* albumin*, rheopolyglucin*, 1.5% reamberin solution*, 10% glucose solution* at the rate of 100-200 ml/kg per day, depending on age and diuresis;

* proteolysis inhibitor aprotinin (for example: trasylol 500,000*, gordox*, contrical*) in an age-related dose;

“■ lasix* 2-3 mg/kg and mannitol 0.5-1 g/kg intravenously in a slow stream to enhance diuresis;

■o- according to indications (disseminated intravascular coagulation syndrome) sodium heparin 100-300 IU/kg intravenously.

To prevent the absorption of toxic metabolites from the intestine resulting from the vital activity of microbial flora, high cleansing enemas, gastric lavage are prescribed, and broad-spectrum antibiotics (gentamicin, polymyxin) are administered.

They report the positive effect of the multienzyme drug Wobenzym*, which has an anti-inflammatory immunomodulatory effect and improves microcirculation.

Taktivin* is prescribed 2-3 ml daily for 10-12 days in order to normalize the quantitative and functional parameters of immunity and prevent complications associated with concomitant infectious diseases.

If the complex of therapeutic measures is ineffective, repeated sessions of plasmapheresis should be performed. Repeated hemosorption sessions and replacement blood transfusions are less effective.

It is advisable to include hyperbaric oxygenation in the complex of pathogenetic agents (1-2 sessions per day: compression 1.6-1.8 atm, exposure 30-45 minutes).

The success of treatment of malignant forms mainly depends on the timeliness of the above therapy. In case of development of deep hepatic coma, therapy is ineffective.