Hepatitis B prevention

Prevention of hepatitis B should be aimed at actively identifying sources of infection, breaking both natural and artificial pathways of infection, as well as increasing immunity to infection through specific prevention.

[1], [2], [3], [4]

Nonspecific prevention of hepatitis B

Neutralization of the source of infection is achieved by the timely detection of all patients and virus carriers, followed by the organization of their treatment and monitoring, completely excluding the possibility of the spread of the disease in the environment of patients.

Early diagnosis of hepatitis B is carried out according to the principles outlined above, and in order to actively detect virus carriers and patients with latent forms of HBV infection, it is recommended to periodically check for high-risk groups for hepatitis B infection. They include first-line patients who received frequent blood transfusions, patients with hemoblastosis and other chronic diseases, as well as specialists serving hemodialysis centers, blood and blood transfusion stations, dentists, etc. The groups of high risk of infection should include the close environment of the source infection in family centers, children's homes and other closed children's institutions,

If a positive result is obtained on the markers of hepatitis B, an emergency notification (Form No 58) is sent to the Sanitary and Epidemiological Station at the place of residence, a special marking of all medical documents relating to this patient is established, followed by medical supervision. Such patients are obliged to follow the rules of personal prophylaxis, preventing the infection of others. Withdrawal of them is possible only after repeated negative blood tests for the presence of HBsAg.

In a system of measures aimed at neutralizing the source of infection, it is very important to carefully examine all categories of donors with mandatory blood testing for each blood donation for the presence of HBsAg and anti-HB co-antibodies by highly sensitive ELISA or RIA methods, as well as to determine ALT activity.

People who have suffered viral hepatitis, people with chronic liver diseases who have had contact with a hepatitis B who received blood and blood transfusions during the last 6 months are not allowed to donate. It is forbidden to use blood and its components for transfusion from donors not examined for hepatitis B markers. It should be borne in mind, however, that donor screening by highly sensitive methods does not completely exclude the danger of them as a source of infection, since in such people antigens of hepatitis B virus can be detected in liver tissue in the absence of them in the blood. That is why to increase the safety of blood preparations it is recommended to examine donors not only for HBsAg, but also for anti-HBe. Elimination of donors from people with anti-HB, regarded as a hidden carrier of HBsAg, virtually eliminates the occurrence of posttransfusinone Hepatitis B.

To prevent infection of newborns, all pregnant women are twice tested on HBsAg by highly sensitive methods: when taking a woman on the register (8 weeks of pregnancy) and on maternity leave (32 weeks). In case of detection of HBsAg, the issue of pregnancy bearing should be decided strictly individually. It is important to consider that the risk of intrauterine infection of the fetus is especially large in the presence of HBeAg in a woman, is negligible in its absence, even if HBsAg is detected in high concentration. The risk of infection of the child is significantly reduced if the birth is performed by a cesarean section.

In order to prevent hepatitis B infection from pregnant women, HBV patients, or carriers of HBV, they are to be admitted to specialized wards of maternity homes, feldsher-midwife stations, where strict anti-epidemic regimens should be provided.

Interruption of transmission routes is achieved through the use of individual syringes, needles, scarifiers, probes, catheters, blood transfusion systems, other medical equipment and equipment used in manipulations associated with disruption of the integrity of the skin and mucous membranes.

If it is necessary to reuse, all medical instruments and equipment must undergo thorough pre-sterilization cleaning and sterilization after each use.

The quality of the tool cleaning is determined with the help of a benzidine or amidopyrine test, which allows to detect the presence of traces of blood. With positive samples, the toolkit is re-processed.

Sterilization of the washed tool can be carried out by boiling for 30 minutes from the boiling point, or by autoclaving for 30 minutes under a pressure of 1.5 atm, or in a dry-fire chamber at a temperature of 160 ° C for 1 hour. Currently, the sterilization of medical instruments is carried out in the central sterilization offices (CSO), which are established with all medical and preventive institutions and operate under the control of the district sanitary epidemiological stations and the administration of medical institutions.

Before the prevention of posttransfusion hepatitis, strict adherence to indications for hemotherapy is very important. Transfusion of canned blood and its components (erythromass, plasma, antithrombin, concentrates VII, VIII) is carried out only for vital indications, which should be reflected in the medical history.

It is necessary everywhere to switch to transfusion of blood substitutes or, in extreme cases, its components (albumin, specially washed red blood cells, protein, plasma). This is due to the fact that, for example, the plasma pasteurization system (60 ° C, 10 h), although it does not guarantee the complete inactivation of the hepatitis B virus, but still reduces the risk of infection; even less risk of infection with transfusion of albumin, protein, and the risk of infection with transfusion of immunoglobulins is negligible.

For the prevention of hepatitis B, transfusion of blood or its components from one ampoule to one recipient, direct transfusion from the parents or from the donor, examined for the presence of HBsAg immediately before the blood, the use of autotransfusions with the advance preparation of the patient's own blood before the operation, etc.,

In the high-risk departments of hepatitis B infection (hemodialysis centers, intensive care units, intensive care units, burn centers, oncological hospitals, hematology units, etc.), hepatitis B prevention is achieved through the strictest implementation of anti-epidemic measures, including the widespread use of single instruments, a fixed group of patients, thorough purification from the blood of complex medical devices, maximum dissociation of patients, restriction of parenter ial interventions and others. In all these cases, HBsAg identification is carried out by highly sensitive methods, and not less than 1 time per month.

To prevent occupational infections, all specialists in contact with blood should use disposable rubber gloves and strictly observe the rules of personal hygiene.

To prevent the spread of infection in families of patients and carriers of HBV current disinfection is carried out, personal hygiene items (toothbrushes, towels, bed linen, sponge, combs, shaving accessories, etc.) are strictly individualized. All members of the family are informed about the conditions under which the infection may occur, and the need to observe personal hygiene rules. For family members of patients with chronic hepatitis B and carriers of HBsAg, medical supervision is established.

Specific prevention of hepatitis B

Specific prophylaxis is achieved by passive and active immunization of children with a high risk of infection.

Passive immunization

For passive immunization, a specific immunoglobulin with a high tiger antibody content of HBsAg is used (titer in the passive hemagglutination reaction is 1/100 thousand-1 / 200,000). As a starting material for the preparation of such an immunoglobulin, a plasma of donors is usually used, in whose blood anti-HBs are detected in the high tiger. Immunoglobulin prophylaxis is recommended:

• children born to mothers who are carriers of HBsAg or patients with acute hepatitis B in recent months of pregnancy (immunoglobulin is administered immediately after birth, and then again at 1, 3 and 6 months);
• after getting into the body of a virus-containing material (blood or its components are transfused from a patient with hepatitis B or an HBV carrier, accidental cuts, injections with an alleged contamination of a virus-containing material, etc.). 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 (patients entering hemodialysis centers, patients with hemoblastoses, etc.) - repeatedly at different intervals (1-3 months or every 4-6 months).

The effectiveness of passive immunization depends primarily on the timing of the introduction of immunoglobulin. When administered immediately after infection, the prophylactic effect reaches 90%, within a period of up to 2 days - 50-70%, and after 5 days immunoglobulin prophylaxis is practically ineffective. With intramuscular injection of immunoglobulin, the peak concentration of anti-HBs in the blood is reached after 2-5 days. To quickly obtain a protective effect, you can resort to intravenous immunoglobulin.

It is also important to take into account that the immunoglobulin release period is from 2 to 6 months, but a reliable protective effect is provided only in the 1st month from the moment of administration, therefore, its repeated administration is necessary to obtain a prolonged effect. In addition, the effect of immunoglobulin is observed only at a low infectious dose of HBV. In case of massive infection (blood transfusion, plasma, etc.), immunoglobulin prophylaxis is ineffective.

It became obvious that the solution of the hepatitis B problem is possible only through mass immunization.

Characteristics of vaccines against hepatitis B

There are two types of hepatitis B vaccine.

1. Inactivated vaccines obtained from HBsAg carrier plasma containing 20 μg of HBsAg (protein) in 1 dose (1 ml). These vaccines do not currently apply.
2. Recombinant vaccines for the production of which recombinant technology is used to incorporate the subunit of the hepatitis B virus gene responsible for the production of HBsAg into yeast or other cells. After the yeast cultivation process is completed, the accumulated protein (HBsAg) is thoroughly purified from yeast proteins. As a sorbent, aluminum hydroxide is used, and as a preservative, the merthiolate.

In Russia, a recombinant vaccine against hepatitis B has been established and its production has been set up at JSC Kombirotekh NPK. The development of the first domestic recombinant yeast vaccine against hepatitis B was completed in 1992 and after a full cycle of state tests conducted by the GISK them. L.A. Tarasevich is included in the State Register of Medicines. The vaccine is produced in 1 ml vials containing HBsAg 20 μg (adult dose) and 0.5 ml with HBsAg 10 μg (infant dose). Preservative - Merthiolate in a concentration of 0.005%. Shelf life of the vaccine is 3 years. The vaccine, according to its characteristics, meets the requirements of WHO and is not inferior to foreign analogues registered in the Russian market.

Recently, two more domestic vaccines against hepatitis B have been registered:

• vaccine against hepatitis B DNA recombinant production of FSUE NPO "Virion" (Tomsk);
• regevak In the production of ZAO "Medico-Technological Holding"

In addition, several foreign vaccine preparations have been registered:

• Engerix B manufactured by GlaxoSmith Klein (Belgium);
• Euwax B vaccine (South Korea);
• hepatitis B vaccine, recombinant NV VAK II, manufactured by Merck Sharp and Dome (USA);
• vaccine shanwak-B of the firm "Shanta-Biotechgnks PVTLTD" (India).

In the last few years, new associated vaccines have been developed and approved in Russia; combined vaccine against hepatitis B, diphtheria and tetanus (bubo-M), combined hepatitis A and B vaccine, combined hepatitis B, diphtheria, tetanus and pertussis vaccine (bubo-coca).

[5], [6], [7], [8], [9], [10], [11], [12],

Hepatitis B Vaccination Schemes

To create a lasting immunity, a triple reduction of the vaccine is necessary. The first two injections can be considered as initial doses, while the third one serves to enhance the production of antibodies. The injection schedule can vary significantly, with the second injection usually done 1 month after the first, and the third - 3 or 6 months after the second. In some cases it is possible to resort to an accelerated mode of vaccination, for example, according to the scheme of 0-1-2 months or 0-2-4 months. At the same time, an earlier formation of a protective level of antibodies in a larger number of patients is noted. When regimens with a longer interval between the second and third injections (for example, 0-1-6 or 0-1 -12 months) are used, seroconversion occurs in the same number of patients, but the antibody titer is higher than with the appointment of accelerated vaccination regimens. The dose of the vaccine is calculated by age, taking into account the drug used.

In many countries, hepatitis B vaccination is included in the vaccination schedule and begins immediately after birth and is performed according to the 0-1-6 month schedule. In some countries, vaccination is only carried out in at-risk groups (medical workers, primarily surgeons, dentists, midwives, blood transfusion service workers, patients on hemodialysis or who often receive 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 that 0.5 ml of immunoglobulin against hepatitis B virus (not mandatory in recent years) be introduced immediately after birth (no later than 48 hours) and proceed to triple immunization with the vaccine scheme 0-1-6 months.

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

Currently, according to the Russian calendar, newborns from at-risk groups are vaccinated according to the 0-1-2-12 month schedule.

For children not at risk, vaccination against hepatitis B is carried out according to the scheme 0-3-6 (the first dose - at the time of vaccination, the second - 3 months after the first inoculation, the third - after 6 months from the start of immunization).

Post vaccination immunity

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

The vaccination effectiveness index ranged from 7.8 to 18.1, but in patients with hemodiatic units it was only 2.4.

Based on the generalized experience with the use of the Engjerix B vaccine in 40 countries around the world, WHO concluded that the seroconversion rate after the introduction of 3 doses in the 0-1-2 or 0-1-6 month schedule approaches 100%. The introduction of the third dose at the 2nd month, in comparison with the administration of the third dose at the 6th month, leads ultimately to a less significant increase in antibody titers, so an immunization schedule of 0-1-6 months may be recommended for routine vaccination, while the 0-1-2 month schedule - in those cases when it is necessary to quickly achieve a sufficient degree of immunity. Later in these children, a more reliable level of antibodies can be achieved by administering a booster dose at 12 months.

It is more difficult to decide the duration of postvaccinal immunity. According to most literature sources, the level of antibodies in the complete three-time vaccination rapidly decreases within the first 12 months after vaccination, then the level decrease occurs more slowly. Most authors are inclined to believe that, most likely, there is no need to conduct revaccination of patients with high seroconversion rates (above 100 IU / d). It is suggested that the immunological memory of the body is the same reliable protection against HBV infection, as well as the regular administration of maintenance doses of the vaccine. The UK Ministry of Health believes that as long as the issue of the duration of immunocompromised immunity has not been fully clarified, it should be considered expedient to revaccinate patients with a level of protection below 100 IU / L.

Vaccination reactions and complications after vaccination against hepatitis B

Recombinant hepatitis B vaccines are slightly reactogenic. Only in single patients there is a reaction at the injection site (mild hyperemia, less frequent edema) or the 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 (Engerix B, etc.), local responses (tenderness, hypersensitivity, pruritus, erythema, ecchymosis, swelling, nodulation) occur in 16.7% of the vaccinated; Among the common reactions, asthenia is noted in 4.2%, malaise in 1.2, an increase in body temperature in 3.2, nausea in 1.8, diarrhea in 1.1, headache in 4.1%; there may also be excessive sweating, chills, hypotension, Quincke's edema, decreased appetite, arthralgia, myalgia, etc.

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

Precautions and contraindications for vaccination against hepatitis B

Constant contraindications to the vaccination against hepatitis B are not available, however, in people with hypersensitivity to any component of the vaccine (for example, the baker's yeast protein), and also in the presence of a serious infectious disease, vaccination should be postponed or canceled,

With some caution should be vaccinated against hepatitis B in patients with severe cardiovascular failure, patients with chronic kidney disease, liver, CNS. However, such conditions do not serve as a contraindication to the introduction of recombinant vaccines, and given that these patients are particularly often infected with hepatitis B with various parenteral manipulations during the examination and treatment, it becomes apparent that they must be vaccinated first.

We must take into account the fact that in patients with immunodeficient conditions (malignant neoplasms, hemoblastoses, congenital and acquired immunodeficiencies, etc.) and in patients who are on immunosuppressive therapy, an increase in the frequency of administration of the vaccine is required to create strained immunity (Scheme 0-1-3 -6-12 months).

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

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

The implementation of the Russian program of hepatitis B vaccine prophylaxis, starting from the neonatal period, invariably poses the question of combining the vaccine with other vaccines before each pediatrician, and first of all with the BCG vaccine. From a scientific point of view, the fear of the incompatibility of these vaccines is completely unfounded, since it is known that the increase in the level of protection when BCG vaccine is administered is achieved through the formation of cellular immunity by the type of postvaccinal allergy, while the introduction of a vaccine against hepatitis B generates humoral immunity.

Studies show that when yeast recombinant vaccine Enzheriks B is injected in the first 24-48 hours of life and vaccination on the 4th-7th day against tuberculosis, no side effects are observed, while 95.6% of children have developed protective immunity against hepatitis B and not there was a significant reduction in the level of protection against tuberculosis, which could be judged from the stable incidence of tuberculosis after the onset of mass vaccination against hepatitis B

On the other hand, the introduction of a hepatitis B vaccine right after the birth of a child is justified only in those cases where there is a high risk of infection of the child in childbirth or immediately after birth, that is, in children born from mothers who are carriers of the hepatitis B virus or hepatitis B, as well as 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, and others.

Of course, it can theoretically be assumed that if the pregnant woman does not have hepatitis B markers (HBsAg, anti-HBcoru), then the vaccination in newborns can be delayed for later periods of life. But with this approach, there can be no assurance that there will be no infection and post-natal period: the Fermentation House, the Department of Neonatal Pathology, etc. That is why in regions with a high level of HBsAg carriage, it is undoubted to start vaccination immediately after birth and regardless of whether or not hepatitis B markers are detected in the mother.

Prior to vaccination against hepatitis B, children from families with HBsAg carriers or patients with hepatitis B are also subject to the data. According to research, in families where there is a source of infection, HBV-markers are found in 90% of mothers, 78.4% of fathers and 78, 3% of children. A similar pattern can be traced in the children's homes and boarding schools, that is, in institutions where there is close contact and the probability of transmission of infection is so-called contact, through microtraumas, household items, etc. It is better to vaccinate gray negative children in such outbreaks after a mass examination children on the markers of hepatitis B. If for some reason it is impossible to determine the markers of hepatitis B, vaccination can be carried out without waiting for the results of the examination. At the same time, one should not exaggerate the negative consequences of administering the vaccine to children (and adults) who have post-infection immunity or even an active infection. The introduction of an additional dose of the 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 the immunizing antigen exerts a booster effect, and there are practically no side effects.

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

The order of the Ministry of Health "On the introduction of preventive vaccinations against hepatitis B" provides for mandatory vaccination of patients who regularly receive blood and its products, as well as those on hemodialysis. Vaccination in these cases should be performed four times in the 0-1-2-6 month schedule, while in patients , which are on hemodialysis, the vines of the vaccine are doubled.

Vaccination of children from 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 the research, in a single screening test, hepatitis B markers are found in 60.2% of patients with hemoblastoses, 36.5 - with solid tumors, 85.2 - with hemophilia and only 6% of patients with acute intestinal infection, and children from families at home maintenance - in 4,3% of cases. It would seem that patients with hemoblastoses, solid tumors and hemophilia should be vaccinated in the first place, but it is known that in conditions of immunodeficiency, the development of immunity for the administration of the vaccine is significantly slowed down or the protective level of antibodies is not formed at all. Our data confirm the low level of protection in response to the introduction of hepatitis B vaccine in patients with hemoblastosis, but taking into account the high risk of infection and the consequences of infection with hepatitis B virus, it is recommended to vaccinate against hepatitis B as soon as a cancer is diagnosed. Vaccination in such patients should be carried out before the emergence of protective immunity according to the scheme: 0-1-3-6-12 or 0-1-2-3-6-12 months.