Hepatitis B is an acute or chronic liver disease caused by the hepatitis B DNA 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 a person. The main reservoir is "healthy" virus carriers; patients with acute and chronic forms of the disease are less important.

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 parenteral route: by transfusion of infected blood or its preparations (plasma, erythrocyte mass, 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 sounding and other manipulations, during which the integrity of the skin and mucous membranes is violated.

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

Infection of children from mothers - carriers of HBV occurs mainly during childbirth as a result of contamination from amniotic fluid containing blood through the macerated skin and mucous membranes of the child. In rare cases, infection of the child occurs immediately after birth through close contact with an infected mother. The transmission of infection in these cases is carried out through microtrauma, i.e. parenterally, and, possibly, by breastfeeding. Infection of the child occurs, most likely, not through milk, but as a result of the mother's blood (from nipple cracks) getting on the macerated mucous membranes of the oral cavity of the child.

The susceptibility of the population to the hepatitis B virus, apparently, is universal, and the outcome of a person's encounter with the virus usually becomes an asymptomatic infection. The frequency of atypical forms cannot be accurately recorded, but judging by the identification of seropositive individuals, then for each case of overt hepatitis B there are tens and even hundreds of subclinical forms.

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

PREVENTION

First of all, it consists in a thorough examination of all categories of donors with a mandatory blood test for HBsAg at each donation using highly sensitive methods for its identification (ELISA, RIA), as well as the 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 blood transfusions and its components within the last 6 months are not allowed to donate. It is forbidden to use for transfusion blood and its components from donors who have not been tested for HB^Ag.

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

To prevent infection of newborns, all pregnant women are examined twice for HBjAg by highly sensitive methods: when registering a pregnant woman (8 weeks of pregnancy) and when taking maternity leave (32 weeks). If HBsAg is detected, the issue of carrying a pregnancy should be decided strictly individually. It is important to bear in mind that the risk of intrauterine infection of the fetus is especially high in the presence of HBjAg in a woman and is negligible in its absence, even if HBjAg is found in high concentrations. The risk of infection of the child is also significantly reduced during delivery by caesarean section.

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

All reusable medical instruments and equipment must be thoroughly pre-sterilized cleaned and sterilized after each use.

For the prevention of post-transfusion hepatitis, strict adherence to 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 the transfusion of blood substitutes or, in extreme cases, to transfuse its components (albumin *, specially washed erythrocytes, protein, plasma). This is due to the fact that plasma pasteurization (60 °C, 10 h), although it does not guarantee complete inactivation of HBV, still reduces the risk of infection; the risk of infection is even less when transfusing albumin*, protein, and the risk of infection is negligible when transfusing immunoglobulins.

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

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

To prevent the spread of infection in the families of hepatitis patients and HBV carriers, current 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 observation.

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 1:100,000-1:200,000). Such an immunoglobulin is obtained from the plasma of donors in whose blood anti-HB is detected. in high titer.

Indications for immunoglobulin prophylaxis in children.

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

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

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

The period of excretion of immunoglobulin 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 the case of massive infection (blood transfusion, plasma, etc.), immunoglobulin prophylaxis is ineffective.

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

temporary administration of a specific immunoglobulin can prevent hepatitis B infection in 70-90% of those vaccinated.

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

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

Active immunization against hepatitis B is subject to:

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

♦ newborns in areas endemic for hepatitis B, with an HBsAg carrier level of more than 5%;

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

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

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

♦ persons who have been 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 scheme 0, 1, 6 months, 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 (HB^g, anti-HBc, anti-HB5) are subject to active immunization. In the presence of one of the markers of hepatitis B, vaccination is not carried out.

The effectiveness of vaccination is very high. Numerous studies show that when the vaccine is administered according to the scheme of 0.1.6 months, protective immunity is formed in 95% of individuals, providing reliable protection against HBV infection for 5 years or more.

There are no contraindications to hepatitis B vaccination. The vaccine is safe, areactogenic. With the help of vaccination, it is possible to 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 the mode of 0.1, 2 months with revaccination at 12 months. This passive-active immunization reduces the risk of infant infection in mothers with HBEAg from 90% to 5%.

The widespread introduction 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 by type, severity, and course. The criteria for determining the type and allocation of clinical forms are the same as for hepatitis A. However, along with mild, moderate and severe forms, a malignant form is also distinguished, which is observed almost exclusively in hepatitis B and delta hepatitis, and the course, in addition to acute and protracted, is chronic.

Clinical and laboratory criteria for anicteric, obliterated, subclinical, as well as mild, moderate and severe forms in hepatitis B do not fundamentally differ from those in hepatitis A.

ETIOLOGY

The causative agent is a DNA-containing virus from the hepadnavirus family (from 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 7-8 nm thick. In the center of the nucleocapsid is the virugya gene, represented by double-stranded DNA.

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

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

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

♦ HBsAg - surface (Australian antigen) that forms 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 lasts 3-6 months, in the refrigerator - 6-12 months, in frozen form - up to 20 years; in dried plasma - 25 years. The virus is extremely resistant to exposure chemical factors: 1-2% solution of chloramine kills the virus after 2 hours, 1.5% formalin solution - after 7 days. 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:

♦ the introduction of the pathogen - infection;

♦ fixation on the hepatocyte and penetration into the cell;

<>reproduction and isolation of the virus on the surface of the hepatocyte. and also in

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

♦ damage to extrahepatic organs and systems;

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

CLINICAL PICTURE

In typical cases of the disease, four periods are distinguished: incubation, initial (preicteric), 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 infectious 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 duration of the incubation period is 4-6 months. In children of the first months of life, the incubation period is usually shorter (92.8±1.6 days) than in older children (117.8±2.6 days).

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

The initial (oredzheltushny) period. The disease 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 be noted lethargy, weakness, increased fatigue, loss of appetite. Often these symptoms are so mild that they are overlooked, and the disease seems to begin with darkening of the urine and the appearance of discolored feces. In rare cases, the initial symptoms are pronounced: nausea, repeated vomiting, dizziness, drowsiness. Often there are dyspeptic disorders: loss of appetite up to anorexia, aversion to food, nausea, vomiting, flatulence, constipation, less often diarrhea. Older children complain of dull pains in the abdomen. Examination during this period may reveal general asthenia, anorexia, enlargement, induration, and tenderness of the liver, as well as darkening of the urine and often discoloration of the feces.

Musculo-articular pains, often found in adult patients, are very rare in children in the preicteric period.

Rarely in the preicteric period, skin rashes, flatulence, stool disorder are observed.

Catarrhal phenomena are generally not 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 a slight leukocytosis, a tendency to lymphocytosis can be noted; ESR is always within the normal range.

In all patients, already in the preicteric period, high activity of ALT, ACT 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 sedimentary samples, as a rule, do not change, there is no dysproteinemia. High concentrations of HB5Ag, HBpAg, anti-HBc IgM circulate in the blood, and viral DNA is often detected.

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

Icteric period (height of the disease). 1-2 days before the onset of jaundice, patients note darkening of the urine and, in most cases, discoloration of the feces. Unlike hepatitis A in hepatitis B, the transition of the disease to 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 increase.

Jaundice increases gradually, usually within 5-7 days, sometimes 2 weeks or longer. Jaundice can vary from a faint yellow, canary or lemon yellow to a greenish yellow or ocher yellow, saffron color. 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, hepatitis B jaundice usually stabilizes within 5-10 days, and only after that does it begin to decrease.

Rashes on the skin can be considered a rare symptom of hepatitis B in children. The rash is located symmetrically on the limbs, buttocks and trunk, it is maculopapular, red, up to 2 mm in diameter. When squeezed, the rash takes on an ocher color, after a few days a slight peeling appears in the center of the papules. These rashes should be interpreted as the Gianotti-Crosti syndrome described by Italian authors in 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 in hepatitis B, the liver enlarges, its edge thickens, and pain occurs on palpation.

Enlargement of the spleen is less common than enlargement of the liver. The spleen is more often enlarged in more severe cases and with a long course of the disease. Enlargement of the spleen is noted during the entire acute period with a slow reverse dynamics. Often, the spleen is palpable even after the disappearance of other (with the exception of an enlarged liver) symptoms, 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 erythrocytes 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.

In the icteric period, the number of leukocytes is normal or reduced. In the leukocyte formula at the height of toxicosis, a tendency to neutrophilosis is revealed, and in the recovery period - to lymphocytosis. ESR is usually within the normal range. Low ESR (1-2 mm / h) with severe intoxication in a patient with severe hepatitis B is an unfavorable sign.

Reconvalescent, recovery period. The total duration of the icteric period in 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 persists, and in 2D - slight hyperfermentemia. The thymol test may be increased, dysproteinemia, etc., are possible.

In the convalescent period, HBsAg and especially HBeAg are usually not detected in the blood serum. but they always find anti-HBE, anti-HBj. 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. Distinguish the initial period of the disease, or the period of precursors, the period of development of massive necrosis of the liver, which usually corresponds to the 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, sometimes drowsiness appear, followed by bouts of anxiety or motor excitement. Dyspeptic disorders are expressed: nausea, regurgitation, vomiting (often repeated), sometimes diarrhea.

With the appearance of jaundice, the most permanent symptoms are: psychomotor agitation, repeated vomiting with blood, tachycardia, rapid toxic breathing, bloating, severe hemorrhagic syndrome, fever 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 of consciousness occurs with clinical symptoms of hepatic coma.

Among the biochemical indicators, the most informative are;

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

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

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

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

Specific recommendations regarding the motor regimen, therapeutic nutrition and criteria for their expansion are in principle the same. as in hepatitis A; it should only be taken into account that the terms of all restrictions for hepatitis B are usually somewhat longer in full accordance with the course of the disease.

In general, it can be said that with a smooth course of the disease, all restrictions in the motor mode and nutrition should be removed 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 1 million units 1-2 times a day for 15 days.

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

In severe forms of the disease, for the purpose of detoxification, intravenous administration of a 1.5% solution of reamberin *, reopoliglyukin \ 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 dose reduction (course no more than 7-10 days). In children of the 1st year of life, moderate forms of the disease are also indications for the appointment of glucocorticoids.

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

* glucocorticoids up to 10-15 mg / kg per day for prednisolone intravenously in equal doses after 3-4 hours without a night break;

* albumin*, rheopolyglukin*, 1.5% solution of reamberin*, 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*) at an age dose;

“■ lasix* 2-3 mg/kg and mannitol 0.5-1 g/kg intravenously bolus slowly to increase diuresis;

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

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

The positive effect of the polyenzyme preparation Wobenzym*, which has an anti-inflammatory immunomodulatory effect and improves microcirculation, is reported.

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. Less effective are repeated sessions of hemosorption and exchange transfusions.

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

Despite the heated public discussion about the necessity/harmfulness of vaccines, it has been convincingly proven that today there is no other protection against dangerous infectious diseases, except for vaccinations.

Vaccination against hepatitis B is carried out according to a certain scheme and is one of the most important in a person's life: this vaccine is given the very first, within 24 hours from the moment of birth.

Few people know about the vaccination schedule for adults. Meanwhile, this disease is one of the most common in the human population, and every person is at risk of contracting it during his life. Consider the scheme of vaccination against hepatitis B for children and revaccination for adults.

The essence of any vaccination is the introduction into the body:

• weakened or inactivated microorganisms - 1 generation of vaccines;
• toxoids (neutralized exotoxins of microorganisms) - 2nd generation of vaccines;
• viral proteins (antigens) - 3rd generation of vaccines.

The preparation administered during vaccination against hepatitis B belongs to the 3rd generation and is a vaccine containing surface antigens s (HBsAg) synthesized by recombinant yeast strains.

The genetic structure of yeast cells (Saccharomyces cerevisiae) is preliminarily subjected to a change (recombination), as a result of which they receive a gene encoding the hepatitis B surface antigen. Further, the antigen synthesized by yeast is purified from the base substance and supplemented with excipients.

After the introduction of the vaccine into the body, antigens cause an immune system reaction, which is expressed in the production of antibodies corresponding to this antigen - immunoglobulins. These immune cells are the "memory" of the immune system. They remain in the blood for years, providing an opportunity to trigger a timely protective reaction if the real hepatitis B virus enters the body. Thus, vaccination, as it were, "trains" the immune system to recognize the dangers to which it must respond.

However, like any training, training the immune system requires repetition. For the formation of stable immunity in both adults and children, it is necessary to carry out several vaccinations against hepatitis B according to the vaccination schedule.

Hepatitis B vaccination schedule

In the territories of the countries of the former USSR, the hepatitis B vaccination schedule is used, which began to be applied in 1982. In accordance with it, all children are subject to vaccination:

• on the first day after birth;
• one month after birth;
• 6 months after birth.

Thus, for the formation of stable and long-lasting immunity, the hepatitis B vaccination scheme involves its threefold administration.

This rule does not apply to children at risk, i.e., born to mothers infected with the virus. In these cases, the hepatitis B vaccination schedule is as follows:

• in the first 24 hours - the first vaccine + antibodies to hepatitis B are additionally introduced (the so-called "passive immunization", designed to protect the child until the development of its own antibodies in response to the vaccine);
• one month after birth - the second vaccine;
• two months after birth - the third vaccine;
• 12 months after birth - the fourth vaccine.

Acquired immunity persists for at least 10 years. However, this indicator is quite variable and can fluctuate in different people.

Vaccination schedule

There are three vaccination schedules that give hepatitis B vaccines to adults. We discussed the first two in the previous paragraph:

• standard scheme of three vaccinations 0-1-6 (the second and third vaccinations are given 1 and 6 months after the first);
• an accelerated schedule of four vaccinations 0-1-2-12 (after 1, 2 and 12 months, respectively).

There is also the option of emergency immunization, which involves 4 vaccinations against hepatitis B for adults according to the scheme 0-7 days - 21 days - 12 months. Such a vaccination schedule is used in emergency cases, when, for example, a person needs to urgently leave for an epidemiologically dangerous region for hepatitis.

The correct use of any of the schemes forms a stable and long-lasting immunity in an adult. An accelerated or emergency hepatitis B vaccination schedule allows you to speed up the process at the beginning, that is, to get sufficient protection by the end of the second (with an accelerated scheme) or by the end of the first (with an emergency scheme) month. However, the fourth vaccination, carried out after 12 months, is necessary for the formation of full-fledged long-term immunity.

Hepatitis B vaccination schedule

What if one of the injections was not done on time?

Compliance with the vaccination schedule for hepatitis B is a mandatory requirement for vaccination. Skipping a vaccination will not allow immunity to form.

A slight deviation from the vaccination schedule of a few days will not affect the antibody titer, stability and duration of acquired immunity.

If for some reason there has been a deviation from the hepatitis B vaccination schedule, the next vaccine should be given as soon as possible.

If there is a significant deviation from the vaccination schedule (weeks or months), you should visit a doctor and get a face-to-face consultation on further actions.

Revaccination scheme

The hepatitis B vaccination schedule for adults involves revaccination approximately once every 10 years until the age of 55, and, according to additional indications, at a later age.

In some cases, for example, when an adult is not sure whether he was vaccinated against hepatitis B and how long ago this could have happened, it is recommended to donate blood for the presence of antibodies to the surface and core proteins of hepatitis (HBsAg and HBcAg).

The amount of anti-HBs shows the intensity of immunity to the hepatitis virus. Vaccination is indicated when the level of antibodies is less than 10 units / l, which is interpreted as a complete lack of immunity to viral antigens.

If antibodies to the nuclear antigen (anti-HBc) are detected, vaccination is not carried out, since the presence of these immunoglobulins indicates the presence of the virus in the blood. Additional studies (PCR) can provide a final clarification.

Revaccination against hepatitis B for adults is carried out according to the standard scheme of three vaccinations 0-1-6.

What vaccines are available for hepatitis B?

Today, a wide range of both mono- and polyvalent hepatitis B vaccines for adults and children is on the market.

Russian-made monovaccines:

• Combiotech;
• Microgen;
• Regevak.

Monovaccines produced by foreign laboratories:

• Engerix V (Belgium);
• Biovac-V (India);
• Gen Wak V (India);
• Shaneak-V (India);
• Eberbiovak NV (Cuba);
• Euwax V (South Korea);
• NV-WAKS II (Netherlands).

The listed vaccines are of the same type: they contain 20 μg of viral antigens in 1 ml of solution (1 dose for an adult).

Since in adults the immunity to many infections acquired in childhood has time to fade away, it is advisable to revaccinate against hepatitis B according to the above scheme using polyvaccines.

Among such polio vaccines for adults can be named:

• against diphtheria, tetanus and hepatitis B - Bubo-M (Russia);
• against hepatitis A and B - Hep-A + B-in-VAK (Russia);
• against hepatitis A and B - Twinrix (Great Britain).

Existing Hepatitis B Vaccines

Is the vaccine safe?

During the use of the vaccine, more than 500 million people have been vaccinated. At the same time, no serious side effects or negative effects on the health of either adults or children were recorded.

Opponents of vaccination, as a rule, refer to the unsafety of the preservative ingredients in the composition of the drug. In the case of hepatitis vaccination, such a preservative is a mercury-containing substance - merthiolate. In some countries, such as the United States, merthiolate vaccines are prohibited.

Reliable data have not been obtained that 0.00005 g of merthiolate - namely, this much is in one injection of the vaccine - would have an impact on human health.

In any case, today it is possible to vaccinate an adult with a drug without a preservative. Combiotech, Engerix B and HB-VAKS II vaccines are produced without merthiolate or with a residual amount of not more than 0.000002 g per injection.

To what extent can vaccination prevent infection?

Vaccination against hepatitis B, carried out in accordance with the scheme for people who do not suffer from immunodeficiency, prevents infection in 95% of cases. Over time, the intensity of immunity to the virus gradually decreases. But in any case, even if a person gets sick, the course of the disease will be much easier, and recovery will be complete and it will happen faster. Read about how the disease is transmitted.

Useful video

For more information about hepatitis B vaccination, see the following video:

Conclusion

1. Vaccination against hepatitis B, made according to the scheme, is the only, almost one hundred percent way.
2. Vaccination is mandatory for children in the first year of life.
3. Revaccination of adults is carried out at will (unless there are indications to the contrary).
4. The standard vaccination schedule includes 3 vaccines on the hepatitis B vaccination schedule (0–3–6 months).
5. Acquired immunity lasts approximately 10 years.

Neutralization of the source of infection is achieved by timely detection of all patients and virus carriers, followed by the organization of their treatment and monitoring, which completely excludes the possibility of spreading the disease among patients.

Hepatitis B vaccination schedules

To create a lasting immunity, a three-fold mixing of the vaccine is necessary. The first two injections can be considered as initial doses, while the third serves to enhance antibody production. The scheme of administration can vary significantly, with the second injection usually given 1 month after the first, and the third - 3 or 6 months after the second. In some cases, you can resort to an accelerated vaccination regimen, for example, according to the scheme 0-1-2 months or 0-2-4 months, while there is an earlier formation of a protective level of antibodies in a larger number of patients. When using regimens with a longer interval between the second and third injections (for example, 0-1-6 or 0-1-12 months), seroconversion occurs in the same number of patients, but the antibody titer is higher than when prescribing accelerated vaccination regimens. The dose of the vaccine is calculated by age, taking into account the drug used.

In many countries, vaccination against hepatitis B is included in the vaccination schedule and begins immediately after birth and is carried out according to the scheme 0-1-6 months. In some countries, vaccination is carried only in risk groups (medical workers, primarily surgeons, dentists, obstetricians, blood transfusion workers, patients on hemodialysis or frequently receiving blood products, etc.). Children born to mothers who are carriers of the hepatitis B virus are subject to mandatory vaccination. In these cases, it is recommended immediately after birth (no later than 48 hours) to administer 0.5 ml of immunoglobulin against the hepatitis B virus (in recent years, optional) and proceed with a triple immunization with the vaccine according to scheme 0-1-6 months.

The hepatitis B vaccine is administered intramuscularly only, in adults and older children it should be administered in the deltoid region, in young children and newborns it is preferable to inject into the anterior-lateral part of the thigh. Injections of the vaccine into the gluteal region are undesirable due to a decrease in the intensity of immunity.

Currently, according to the national calendar, newborns from risk groups are vaccinated according to the scheme 0-1-2-12 months of life.

Children who do not belong to risk groups are vaccinated against hepatitis B according to the 0-3-6 scheme (the first dose is at the time of the start of vaccination, the second is 3 months after the first vaccination, the third is 6 months after the start of immunization).

Post-vaccination immunity

According to our clinic, in newborns vaccinated in the first 24 hours of life with the recombinant vaccine Engerix B according to the scheme 0-1-2 months with revaccination at 12 months, seroconversion occurred in 95.6% of cases, while the level of anti-HB after the third dose amounted to 1650+395 IU/l. and before revaccination - 354 + 142 IU / l. After the introduction of a revaccinating dose, the level of antibodies increased by 10 times or more. One month after the completion of the course of vaccination with Engerix B in different groups (newborns, medical workers, students, etc.), a protective antibody titer is detected in 92.3-92.7% of those vaccinated. After 1 year, antibody titers decrease, but remain protective in 79.1-90% of those vaccinated.

The vaccination efficiency index ranged from 7.8 to 18.1, but in patients with hemodiasis departments it was only 2.4.

Based on the generalized experience of using Engerix B vaccine in 40 countries of the world, WHO concluded that the seroconversion rate after administration of 3 doses according to the 0-1-2 or 0-1-6 months regimen approaches 100% Introduction of the third dose at the 2nd month, compared with the introduction of the third dose at the 6th month, ultimately leads to a less significant increase in antibody titers, so the 0-1-6 month immunization schedule can be recommended for routine vaccination, while the 0-1-2 month schedule - in cases where you need to quickly achieve a sufficient degree of immunity. Later, in these children, a more reliable level of antibodies can be achieved with the introduction of a booster dose after 12 months.

It is more difficult to decide on the duration of post-vaccination immunity. According to most literature sources, the level of antibodies after a completed three-time vaccination decreases rapidly during the first 12 months after vaccination, then the level decreases more slowly. Most authors are inclined to believe that, most likely, there is no need to revaccinate patients with high seroconversion rates (above 100 IU/d). At the same time, it is suggested that the body's immunological memory is as reliable a means of protecting against HBV infection as regular administration of maintenance doses of the vaccine. The UK Department of Health believes that until the question of the duration of post-vaccination immunity is finally clarified, it should be considered appropriate to revaccinate patients with protection levels below 100 IU/L.

Vaccination reactions and complications after vaccination against hepatitis B

Recombinant hepatitis B vaccines are not very reactive. Only a few patients have a reaction at the injection site (mild hyperemia, rarely swelling) or a general reaction in the form of a short-term increase in body temperature to 37.5-38.5 ° C.

In response to the introduction of foreign recombinant vaccines (Angerix B and others), local reactions (soreness, hypersensitivity, itching, erythema, ecchymosis, swelling, nodules) occur in total in 16.7% of vaccinated people; among the general reactions, asthenia is noted in 4.2%, malaise - in 1.2, fever - in 3.2, nausea - in 1.8, diarrhea - in 1.1, headache - in 4.1%; increased sweating, chills, hypotension, Quincke's edema, loss of appetite, arthralgia, myalgia, etc. are also possible.

Similar adverse reactions are also described for the introduction of the domestic vaccine combotech. All these reactions do not significantly affect the state of health, are short-lived and, most likely, are caused by the presence of yeast protein impurities in recombinant vaccines.

Precautions and contraindications for hepatitis B vaccination

There are no permanent contraindications to hepatitis B vaccination. However, in people with hypersensitivity to any component of the vaccine (for example, baker's yeast protein), or in the presence of a serious infectious disease, vaccination should be postponed or canceled,

With some caution, vaccination against hepatitis B should be carried out in patients with severe cardiovascular insufficiency, patients with chronic diseases of the kidneys, liver, and central nervous system. However, such conditions do not serve as a contraindication to the introduction of recombinant vaccines, and given that these patients are especially often infected with hepatitis B during various parenteral manipulations during examination and treatment, it becomes obvious that they should be vaccinated in the first place.

It is necessary to take into account the fact that in patients with immunodeficiency states (malignant neoplasms, hemoblastoses, congenital and acquired immunodeficiencies, etc.) and in patients on immunosuppressive therapy, an increase in the frequency of vaccine administration is required to create intense immunity (scheme 0-1-3 -6-12 months).

Vaccination in pregnant women should only be carried out if the potential benefit justifies the possible risk to the fetus.

About combining vaccination against hepatitis B with the introduction of other vaccines

The implementation of the Russian hepatitis B vaccination program, starting from the neonatal period, invariably raises the question of combining the vaccine with other vaccines, and primarily with the BCG vaccine, before each pediatrician. From a scientific point of view, the concern about the incompatibility of these vaccines is unfounded, since it is known that an increase in the level of protection with the introduction of the BCG vaccine is achieved due to the formation of cellular immunity according to the type of post-vaccination allergy, while with the introduction of the hepatitis B vaccine, humoral immunity is formed.

Studies show that the introduction of the recombinant yeast vaccine Engerix B in the first 24-48 hours of life and vaccination on the 4-7th day against tuberculosis do not cause side effects. At the same time, 95.6% of children developed protective immunity against hepatitis B and there was a marked decrease in the level of protection against tuberculosis, as evidenced by the stable incidence of tuberculosis after the start of mass vaccination against hepatitis B

On the other hand, the introduction of hepatitis B vaccine immediately after the birth of a child is justified only in cases where there is a high risk of infection of the child during childbirth or immediately after birth, that is, in children born to mothers who are carriers of the hepatitis B virus or patients with hepatitis B, and also in regions with a high prevalence of HB virus infection. First of all, these are the regions of Siberia, the Far East, the Republic of Tyva, Kalmykia, etc.

Of course, theoretically it can be assumed that if a pregnant woman does not have hepatitis B markers (HBsAg, anti-HBcory), then vaccination in newborns can be delayed to later periods of life. But with this approach, it is impossible to guarantee that infection will not occur in the postnatal period: in the Fermentation House, in the neonatal pathology department, etc. That is why in regions with a high level of HBsAg carriage, undoubtedly, vaccination should be started immediately after birth and regardless whether or not markers of hepatitis B are detected in the mother.

Children from families where there is a carrier of HBsAg or a patient with hepatitis B are also subject to priority vaccination against hepatitis B. According to studies, in families where there is a source of infection, markers of HBV infection are found in 90% of mothers, 78.4% of fathers and 78. 3% of children. A similar pattern can be traced in orphanages and boarding schools, that is, in institutions where there is close contact and a high probability of transmission of infection by the so-called contact route, through microtrauma, household items, etc. It is better to start vaccination of sero-negative children in such foci after a mass examination children for hepatitis B markers. If for some reason it is not possible to determine hepatitis B markers, vaccination can be carried out without waiting for the results of the examination. At the same time, the negative consequences of administering the vaccine to children (and adults) with post-infectious immunity or even active infection should not be exaggerated. The introduction of an additional dose of immunizing antigen in the form of a recombinant vaccine should be regarded as a positive rather than a negative factor, since it is known that an additional dose of immunizing antigen has a booster effect, and adverse reactions are practically absent.

For this reason, attempts are being made to treat chronic hepatitis B or HBsAg carriage by administering a hepatitis B vaccine. According to American pediatricians, the determination of hepatitis B markers may be more expensive than the vaccination itself, since only a positive effect should be expected from the introduction of the vaccine, it is more rational to vaccinate without prior expensive laboratory research.

The order of the Ministry of Health "On the introduction of prophylactic vaccinations against hepatitis B" provides for mandatory vaccination of patients who regularly receive blood and blood products, as well as those on hemodialysis. Vaccination in these cases should be carried out four times according to the scheme 0-1-2-6 months, while in patients who are on hemodialysis, the vines of the vaccine are doubled.

Vaccination of children against hepatitis B with oncohematological diseases

As is known, patients with hemoblastoses, solid tumors and hemophilia during treatment are especially often infected with the hepatitis B virus.

According to studies, with a single screening examination, hepatitis B markers are found in 60.2% of patients with hemoblastoses, in 36.5 - with solid tumors, in 85.2 - with hemophilia, and only in 6% of patients with acute intestinal infection, and in children from families with home maintenance - in 4.3% of cases. It would seem that patients with hemoblastosis, solid tumors and hemophilia should be vaccinated in the first place, however, it is known that in conditions of immunodeficiency, the development of immunity to the vaccine is significantly slowed down or a protective level of antibodies is not formed at all. Our data confirm the low level of protection in response to the hepatitis B vaccine in patients with hemoblastoses, but given the too high risk of infection and the consequences of infection with the hepatitis B virus, it is recommended to vaccinate against hepatitis B as soon as a diagnosis of cancer is made. Vaccination in such patients should be carried out before the appearance of protective immunity according to the scheme: 0-1-3-6-12 or 0-1-2-3-6-12 months.

Foreword……………………………………………………………………………1

Hepatitis A virus……………………………………………………………………2

Transmission method…………………………………………………………………………………………2

Disease……………………………………………………2

Clinical course ............................................................... ..…........3

Treatment...........…………………....................……......... ...........3

Complications...............................……................ .........................3

Prevention ...............................................................…. …....................4

Passive immunization ............................................................................... .........5

Active immunization ..............................................................………................ ....5

Hepatitis A Vaccines ..............................................................……….......... ......................6

Vaccine “HEP-A-in-VAK” .............................................. ......………..........................eight

Production and composition ..............................................................…….. ................................…ten

The effect of the drug .............................................................................. ...........ten

The period of preservation of immunity .............................................. 10

Combination with passive immunization....................................................11

Dosage...........................................…….... ..........................eleven

Indications and use of the drug “HEP-A-in-VAK” ........…….................................11

Contraindications ............................................................................................... ............12

Side effects ............................................................................................... ..........12

And others - "Comparative study of the immunogenicity of the inactivated hepatitis A vaccine "He-A-in-Vac" according to experimental and clinical studies" "Vopr. Virology", 5, 268-270.

, - "Optimization of the conditions for obtaining an inactivated vaccine against hepatitis A and its characteristics" "Vopr. Virology", 6, 215-218, 1995.

And others - "Assessment of the reactogenicity and immunogenicity of the culture concentrated inactivated vaccine against hepatitis A" Hep-A-in-Vak "," Vopr. Virology" 5, 219-220, 1995.

And others - "Study of the domestic cultural concentrated inactivated vaccine against hepatitis A" Hep-A-in-Vac "," Journal of Microbiology ", 1, 50-54, 1998.

, - "On the development of requirements and methods for quality control of the first inactivated vaccine against hepatitis A." in the book "Modern features of the development of the epidemiological process in a big city" - Mat-ly scientific. practical Conf., pp.38-40.-M.1995.

AI, A- "Results of field trials of the domestic vaccine against hepatitis A" Hep-A-in-Vac ", - Materials of scientific. practical conf., pp. 211-212.-M.1997.

G, - "Characterization of the reactogenic and immunogenic properties of the children's version of the domestic vaccine against hepatitis A" Vopr. Virology", 3, 133-138, 1999.

, - "Development of a cultured concentrated purified inactivated vaccine against hepatitis A "Hep-A-in-Vac" - Bulletin "Vaccination" No. 4 (16), July-August 2001

CONTRAINDICATIONS

Acute infectious and non-infectious diseases, exacerbations of chronic diseases. In these cases, vaccination is carried out no earlier than 1 month. after recovery (remission).

Immunodeficiency states, malignant blood diseases and neoplasms.

Strong reaction (temperature above 400C; hyperemia, edema at the injection site with a diameter of more than 8 cm) to the previous Hep-A-in-Vac vaccination.

In order to identify contraindications, the doctor (paramedic) on the day of vaccination conducts an examination and interview of the vaccinated person with mandatory thermometry. If necessary, conduct an appropriate laboratory examination.

SIDE EFFECTS

The drug "HEP-A-in-VAK" does not cause significant side effects. Side effects associated with the use of the drug do not exceed similar indications for other vaccines containing purified antigens adsorbed by aluminum. Of the local side effects, pain in the injection area, a slight increase in temperature and mild malaise are most often noted. Sometimes there is redness, hardening and swelling of the injection site. Local adverse reactions are observed from 4 to 7% of the total number of vaccinated and disappear after 1-2 days.

VACCINE INTRODUCTION TO PREGNANT WOMEN

AND TO NURSING MOTHERS

The effect of the drug on fetal development has not been specifically studied, however, as is the case with all inactivated viral vaccines, the possibility of a negative effect of this vaccine on fetal development is considered negligible. During pregnancy, the drug should be used only if clearly necessary.

DISEASE

The target organ for the hepatitis A virus is the liver, and the primary cells of the lesion are hepatocytes. After ingestion, viral particles are absorbed through the mucous membrane of the gastrointestinal tract and enter the general blood circulation system.

Once in the liver, the virus is recognized by receptor sites on the hepatocyte membrane and taken up by the cells. Inside the cell, the virus decapsidates, the viral RNA is released, and transcription begins. Viral proteins are synthesized and assembled into new capsids, each containing newly replicated strands of viral RNA. The HA virion is packaged in vesicles and released from the cell into the bile ducts, which pass between the hepatocytes. The vesicle membrane dissolves in bile, HAV particles are released, followed by their entry into the feces or infection of neighboring hepatocytes.

CLINICAL COURSE

The typical clinical course of hepatitis A has four stages:

1 incubation period;

2 Prodromal phase;

3. Icteric phase;

4 recovery.

The severity of the disease usually depends on the age of the patient. In young children, it is usually asymptomatic or causes atypical symptoms, often without jaundice. Adults develop symptomatic infection, often with jaundice, which is generally more severe in patients 40 years of age or older.

Disease course and mortality

The average duration of the disease is 27-40 days, with 90% of patients being hospitalized. Within six months after the disease, there is a recovery period, during which it is necessary to comply with the therapeutic and protective regimen, a special diet and medical supervision.

Hepatitis A is fatal in a very small number of cases, most of which are fulminant hepatitis A.

Mortality is higher among people with chronic liver disease who develop acute hepatitis A.

TREATMENT

There is no specific effective treatment for hepatitis A, which is self-limiting, so prevention is the preferred medical intervention.

DOSAGE

Each dose is a sterile suspension of 1.0 ml for adults and 0.5 ml for children. The vaccine should be used as supplied. Strictly observe the recommended doses. The standard course of vaccination of the drug consists of two doses administered at intervals of 6-12 months between the first and second vaccinations. The HEP-A-in-VAK vaccine is for intramuscular injection into the deltoid muscle only.

INDICATIONS AND USE OF THE DRUG
“HEP-A-in-WAC”

Hepatitis A vaccine “HEP-A-in-VAK” is intended for active vaccination against hepatitis A virus.

In areas with a low to moderate prevalence of hepatitis A, vaccination with HEP-A-in-VAK is especially recommended for people who are or will be at increased risk of infection, including the following categories of people:

People traveling to regions with a high prevalence of hepatitis A on business or tourism trips (Africa, Asia, the Mediterranean, the Middle East, Central and South America, Kazakhstan, Turkmenistan, Uzbekistan) are usually at high risk for tourists in these regions due to the following factors :

greens and fruits washed in contaminated water;

uncooked food prepared by an infected person;

bathing in contaminated water;

Military personnel traveling or serving in regions with a high prevalence of hepatitis A and with poor sanitation are at increased risk of contracting hepatitis A. Active vaccination is indicated for them;

People who can become infected with hepatitis A in connection with professional activities and who are at risk of becoming carriers of the virus: kindergarten workers, employees of orphanages and nursing homes, nurses who care for the sick, medical and

attendants of hospitals and other medical institutions, especially gastroenterological and pediatric departments, locksmiths

Currently, the treatment of patients with hepatitis A is supportive and is aimed at ensuring the comfort of the patient and maintaining an adequate balance of nutrients and electrolytes. Most physicians allow patients to eat whatever they like (although fatty foods cause nausea in most patients), as long as the diet contains sufficient fluids, calories, and protein.

PREVENTION

Taking into account the absence of specific means of treatment, as a rule, late, epidemically ineffective hospitalization, as well as the possibility of prolonged treatment and adverse consequences of hepatitis A, the most effective means of combating this infection should be considered its prevention, which is currently most radically provided by vaccination. The possibility of specific prevention of hepatitis A is one of the most important achievements of biology and medicine in recent years. Non-specific prevention of hepatitis A, as a classic cellular infection, rests on the solution of socio-economic, sanitary, hygienic and environmental problems of society and is difficult to achieve.

Planned immunoprophylaxis with the introduction of normal immunoglobulin has a short-term, for 2-3 months, protective effect. in addition, antibodies to hepatitis A in normal immunoglobulin are now often found in low titer. Because of this, passive immunoprophylaxis, which for many years was the only control measure, today does not solve either regional or global problems. These problems are fundamentally solved only by vaccination.

PASSIVE IMMUNIZATION

In the 1940s, researchers discovered that immunoglobulins obtained from convalescent hepatitis A patients who had developed natural immunity contained specific antibodies against the hepatitis A virus. Currently, immunoglobulin series are produced by large-scale separation and concentration of serum proteins from donor plasma . Immunoglobulin is effective only in 85% of cases. The duration of the protective effect during passive immunization is no more than 3-5 months. Currently, passive immunization is used only in some cases for urgent travel to areas endemic for hepatitis A (together with the vaccine) and in children in case of close contact with the patient in the family or child care facility.

safety of sterility and immunogenicity. The production process consists of several main stages:

Production culture-producer.

Infection of the producer culture.

Collection of virus from cell culture.

Purification and concentration.

Complete inactivation of the virus with formaldehyde.

Getting the finished form.

Inactivation is several times higher than the minimum required period of hepatitis A virus inactivation. Purified and inactivated hepatitis A virus after passing all controls is adsorbed on aluminum hydroxide. The vaccine "HEP-A-in-VAK" is a suspension of inactivated, purified hepatitis A virus (HAV) virions adsorbed on aluminum hydroxide, there are no preservatives.

DRUG ACTION

The hepatitis A vaccine creates immunity to infection with the hepatitis A virus by promoting the formation of specific antibodies in the body that act against this virus.

The vaccine stimulates the production of antibodies to the hepatitis A virus in at least 98% of seronegative individuals on days 21-28 after a full course of immunization. The vaccine can be used both for mass immunization and for individual protection against hepatitis A.

IMMUNITY PERIOD

The vaccination course consists of two intramuscular injections of vaccines with an interval of 6-12 months between the first and second vaccinations. By creating persistent active immunity in the vaccinated, the duration of immunity is at least 12-15 years. For groups of people in need of long-term protection, vaccination is a more practical way to obtain it than the introduction of immunoglobulin.

COMBINATION WITH PASSIVE IMMUNIZATION

Both active and passive immunization can be used simultaneously to provide both immediate and long-term protection in humans, and usually an immediate protective effect is achieved. With the parallel use of the vaccine and immunoglobulin, the drugs should be administered in different parts of the body.

Since 1997, the industrial production of the first domestic vaccine "HEP-A-in-VAK" for public health needs has begun.

Since 1997, the first domestic vaccine has been approved by the MIBP committee as a means of active prevention of viral hepatitis A in children from 3 years of age, adolescents and adults. In 1999, GISK them. repeated tests of the HEP-A-in-VAK vaccine were carried out for reactogenicity, harmlessness and immunogenicity on an adult contingent. The results once again confirmed the conclusions made during the State trials of the vaccine in 1992, 1997. The study of immunogenic activity showed that one month after the first trial of the HEP-A-in-VAK vaccine, the seroconversion rate was 75%, while the geometric mean titer (SP) of anti-HAV corresponded to 106.7 mIU/ml, which corresponds to a protective titer antibodies when using the test system ELISA "Vector". One month after the second vaccination, the immunogenicity index was 96.2% seroconversions with GT anti.4 mIU/ml. Currently, according to the NTD approved in 2001 (FSP, RP No. 000-01 and instructions for use), the hepatitis A vaccine "GEP-A-in-VAK" is used to prevent hepatitis A in children from the age of three, adolescents and adults. A full course of vaccination consists of two vaccinations given 6-12 months apart and provides long-term protection against hepatitis A infection. The vaccine provides active immunity against hepatitis A by stimulating the body to produce antibodies against hepatitis A. Considering the relationship between the level of antibodies and the duration of immunity, one can count on the creation of stable immunity lasting at least 10-15 years after a full course of vaccination (two vaccinations). A single injection of the vaccine (1 dose) provides protection for the body for 1-2 years a month after the administration of the drug.

PRODUCTION AND COMPOSITION

For the production of the vaccine "HEP-A-in-VAK" use the strain LBA-86, obtained in IPVE them. RAMN as a result of the adaptation of the HAS-15 strain to the 4647 cell line approved for vaccine production, which meets all the requirements of the World Health Organization. The hepatitis A virus grows very slowly, and it takes about three weeks to reach the harvest stage of the virus grown in cell culture.

The production of a vaccine is not only a lengthy but also a complex process. At all stages of vaccine manufacture, from the production strain to the finished form of the vaccine, a number of known and new physicochemical and molecular biological tests, as well as controls on animals and in cell culture, are provided. This system reliably ensures that the final product meets the requirements of the standards

ACTIVE IMMUNIZATION

It is known that vaccination is one of the main ways in the system of epidemiological measures in the fight against infection. Therefore, in recent years, active research has been carried out in many countries of the world to develop vaccines against hepatitis A.

Hepatitis A vaccines are administered subcutaneously or intramuscularly. It showed that a single injection of the vaccine protects against infection, however, for a longer preservation of immunity, its repeated administration is necessary. As a rule, vaccination of adults and children is carried out twice with an interval of 6-18 months. The introduction of the vaccine leads to the appearance of protective antibodies to the hepatitis A virus on the 15-28th day after vaccination. The resulting protective immunity lasts for a year after the first vaccination. With the introduction of the second dose of the vaccine 6-12 months after the primary immunization, it is possible to prolong immunity to hepatitis A up to 15 years. Mass vaccination against hepatitis A is carried out in Israel, a number of US states and some provinces in Spain and Italy. In 1999, the US government called on all states to include hepatitis A vaccination in their vaccination schedule. The use of the vaccine provides long-term protection.

HEPATITIS A VACCINES

In Russia, vaccines are allowed, which are killed viruses grown in cell culture. To date, the following vaccines have been registered in Russia:

Hepatitis A vaccine culture purified concentrated adsorbed inactivated liquid "Gep-A-in-Vak" CJSC "Vector-BiAlgam" Russia;

Hepatitis A vaccine culture purified concentrated adsorbed inactivated liquid with polyoxidonium "Gep-A-in-Vac-Pol" CJSC "Vector-BiAlgam" Russia;

Avaxim, Aventis Pasteur, France;

"Vakta" 50 units, "Merck, Sharp and Dome", USA;

"Vakta" 25 units, Merck, Sharp and Dome, USA;

Havrix 1440, GlaxoSmithKline, England;

Havrix 720, GlaxoSmithKline, England;

All of these vaccines are based on inactivated hepatitis A antigen adsorbed on aluminum hydroxide.

VACCINE “HEP-A-in-VAK”

In our country, research on the development of approaches to the creation of hepatitis A vaccines was started in the 80s of the 20th century. At the Institute of Poliomyelitis and Viral Encephalitis of the USSR Academy of Medical Sciences, in the laboratory headed by the professor, a scientific basis for such work was created. Methods for cultivating the hepatitis A virus in laboratory conditions were mastered. The HAS-15 strain of hepatitis A virus adapted to growth in cell culture 4647 approved for vaccine production was chosen as the initial strain for obtaining the inactivated vaccine. inactivated vaccine against hepatitis A. After their successful laboratory certification and the first clinical and laboratory tests, the development in its laboratory version was transferred to the SSC VB "Vector", (Novosibirsk), where the development of the technology for the production of an industrial scale vaccine against hepatitis A, corresponding to the requirements of WHO, in order to introduce it into the practice of Russian medicine.

Vaccine production is a complex and lengthy process. At all stages of the preparation of the vaccine, from the production strain to the finished form of the vaccine, a number of modern physicochemical and molecular biological tests, as well as tests on animals and in cell culture, are provided. This system reliably ensures the safety of the vaccine and a high level of its immunological activity. The finished form of the Hep-A-in-Vac vaccine is a suspension of inactivated purified HAV virions adsorbed on aluminum hydroxide, preservatives and antibiotics are absent in the vaccine.

In accordance with the existing regulation on the procedure for registering vaccines, according to the test program approved by the Academic Council of the GISK named after. and the MIBP Committee, were conducted in 1992 State trials of the vaccine on volunteers.

At the first stage, the studies were carried out in a controlled experiment among organized adult contingents. Persons who did not have GA, who did not receive a human immunoglobulin preparation within 6 months before vaccination and did not have contraindications provided for in the instructions for use, were subjected to immunization. The results of the reactogenicity and safety of laboratory series and experimental series of the Hep-A-in-Vac vaccine under the conditions of clinical and laboratory observations did not reveal deviations from the physiological norm in the vaccinated in terms of the cellular composition of peripheral blood, feces, urine, as well as the level of aminotransferases. The specific safety of the drug was also evidenced by statistically insignificant differences in the frequency of somatic infectious morbidity in the experimental and control groups. Moderate reactogenicity of the Hep-A-in-Vac vaccine was manifested by single common

reactions (from 0 to 4%) in the form of fever to subfebrile figures, headache, dizziness. Local reactions were manifested in the form of minor soreness and redness.

When analyzing the results of immunogenic activity, it was found that the full course of immunization with laboratory and experimental series of the Hep-A-in-Vac vaccine provided the formation of anti-HAV antibodies in seronegative volunteers in almost the same percentage of cases (87.3-94.2%) .

The study of the preventive efficacy of the Hep-A-in-Vac vaccine was carried out among organized contingents of people aged 18-21 years with a total of 8260 people. Observation of the vaccinated was carried out for 8 months after the end of the course of immunization during the seasonal rise in the incidence of GA. The vaccine effectiveness rate was 98%

Thus, trials of the HEP-A-in-VAK vaccine showed the almost complete absence of reactogenicity, good drug tolerance, specific safety, high immunological activity, and 98% preventive efficacy of the vaccine. Based on the results of the State Tests, the MIBP Committee recommended the introduction of the GEP-A-in-VAK vaccine into public health practice for vaccination of the adult population.

Taking into account the data of the State trials in adults, the content of aluminum hydroxide in one inoculation dose was reduced from 1.0 to 0.5 mg, and the stabilizer - human serum albumin was also excluded.

Taking into account the changes made in 1995-96, 5 production batches were produced, which passed control in the GISC by him in all quality parameters for these drugs. In 1996, a program of State trials of a domestic vaccine for children was developed and approved. In 1997, under the leadership of GISK, they conducted a study of the drug on the children's contingent. The results obtained confirmed the conclusions about the specific safety, moderate reactogenicity and high immunogenic activity of the first domestic vaccine against viral hepatitis A, made at the first stage. After the second stage, permission was obtained from the MIBP Committee of the Ministry of Health of Russia for the use of the Hep-A-in-Vac vaccine in healthcare practice for mass vaccination of the population from the age of three. Since 1997, the production of a domestic hepatitis A vaccine has been organized, which is still the only domestic vaccine against this infection.

In subsequent years, highly efficient methods for purifying the viral antigen were introduced, which made it possible to reduce the content

cellular DNA from 200 pg/ml to 100 and below pg/ml.

total protein from 125mg/ml to 1mg/ml

These purification methods made it possible to increase the content of HAV antigen in one adult dose from 50 ELISA units to 80 ELISA units. Since the specific activity of most viral inactivated vaccines, including those against hepatitis A, depends on the content of the viral antigen, such an increase made it possible to significantly increase the immunogenicity of the vaccine and switch from triple to double immunization.

In 1999, GISC conducted repeated tests of the Hep-A-in-Vac vaccine for reactogenicity, harmlessness and immunogenicity on an adult contingent. the results once again confirmed the conclusions made during the State tests in 1992 and 1997. The study of immunogenic activity showed that one month after the first immunization with the Hep-A-in-Vac vaccine, the seroconversion rate was 75%, while the geometric mean titer (SGTanti-HAV was 106.7 mIU/ml, which corresponds to the protective antibody titer at using the ELISA test system "Vector" One month after the second vaccination, the immunogenicity index was 96.2% seroversion with GT anti.4 mIU / ml is used to prevent hepatitis A in children from the age of 3 years, adolescents and adults.The full course of vaccination consists of two vaccinations, carried out at an interval of 6-12 months after the first vaccination, provides long-term protection against diseases of viral hepatitis A. The vaccine provides active immunity against hepatitis And by stimulating the production of antibodies against hepatitis A by the body. Given the relationship between the level of antibodies and the duration of immunity, one can count on creating lasting immunity lasting at least 15 years after a full course of vaccination (two shots). A single injection of the vaccine (1 dose) provides protection for the body for 1-2 years a month after the administration of the drug.

Hepatitis B virus causes serum hepatitis (viral liver disease). Its outcome is difficult to predict. In severe and debilitated 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 takes place only in the patient. Therefore, earlier the only way its preparation was the isolation of viral particles from the blood of sick people, and the only vaccine were antibodies isolated from the blood serum of carriers of the virus. 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 a shell and a nucleocapsid with a diameter of 27 nm containing DNA molecules.

Purified nucleocapsid preparations serve material source for vaccine preparation, 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 the Hbs aptigen (HbsAG). The viral envelope probably consists of a lipid bilayer containing polypeptide dimers containing 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. Inside the virions contains 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), fixed length,
• the other is short (S), with variable length.

Transmission of hepatitis B virus in vivo 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 hampered by its narrow specialization. Its genome was cloned and introduced (in whole or in part) into cell lines, after which gene expression was studied. Thus, in 1980, Dubois and his colleagues succeeded in introducing viral DNA into mouse L-cells. They found that the viral DNA integrated into the cellular DNA and that the HbsAG particles were secreted into the culture medium without lysing the mouse cells.

In 1981, Mariarti and his collaborators created hybrid DNA molecule containing DNA of the SV40 virus and a DNA fragment of the hepatitis B virus. When introduced into monkey kidney cells, it caused the synthesis of HbsAG particles. Cloning of viral DNA 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 probably help to obtain other types of antigens, possibly more economical and safer in vaccine production. So, Rutter (USA) received yeast cells that form glycosylated surface antigen. An Hbc protein was also obtained, isolated from viral particles and synthesized under the control of recombinant DNA in bacteria. This protein protected the chimpanzee from subsequent infection with the hepatitis B virus.

Use of Recombinant DNA Technique 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 hepatitis B vaccine. These are two cyclic peptides that have been administered intraperitoneally to mice using various adjuvants. Antibodies to the surface of the hepatitis B virus were detected 7-14 days after immunization.