Hepatitis B prevention

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

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Non-specific prophylaxis of hepatitis B

Neutralization of the source of infection is achieved by timely identification of all patients and virus carriers, followed by organizing their treatment and observation, completely eliminating the possibility of the spread of the disease among the patients.

Early diagnostics of hepatitis B is carried out according to the principles outlined above, and in order to actively identify virus carriers and patients with latent forms of HBV infection, it is recommended to conduct periodic examination of high-risk groups for hepatitis B markers. These include, first of all, patients who have received frequent blood transfusions, patients with hemoblastoses and other chronic diseases, as well as specialists servicing hemodialysis centers, blood transfusion centers, dentists, etc. High-risk groups should also include the close environment of the source of infection in family foci, children's homes and other closed children's institutions,

If a positive result is obtained for hepatitis B markers, an emergency notification (form No. 58) is sent to the sanitary and epidemiological station at the place of residence, special marking of all medical documents related to this patient is issued, and medical observation is established for him. Such patients are required to follow the rules of personal prevention, preventing infection of others. They can be removed from the register only after repeated negative blood tests for the presence of HBsAg.

In the system of measures aimed at neutralizing the source of infection, of great importance is a thorough examination of all categories of donors with mandatory blood testing at each blood donation for the presence of HBsAg and anti-HB core antibodies using highly sensitive ELISA or RIA methods, as well as determination of ALT activity.

Persons who have had viral hepatitis, people with chronic liver diseases, those who have had contact with a patient with hepatitis B, or those who have received transfusions of blood and its components within the last 6 months are not allowed to donate. It is prohibited to use blood and its components from donors who have not been tested for hepatitis B markers for transfusion. It should be borne in mind that testing donors with highly sensitive methods does not completely exclude the danger of them as a source of infection, since hepatitis B virus antigens can be detected in liver tissue in such people without them being found in the blood. That is why, in order to increase the safety of blood products, it is recommended to test donors not only for HBsAg, but also for anti-HBe. Removing people with anti-HB, considered as latent carriers of HBsAg, from donation practically excludes the occurrence of post-transfusion hepatitis B.

To prevent infection of newborns, all pregnant women are tested twice for HBsAg using highly sensitive methods: when a woman is registered (8 weeks of pregnancy) and when she goes on maternity leave (32 weeks). If HBsAg is detected, the question of carrying the pregnancy to term should be decided strictly on an individual basis. It is important to take into account that the risk of intrauterine infection of the fetus is especially high if the woman has HBeAg, and is negligible if she does not, even if HBsAg is detected in high concentrations. The risk of infection of the child is significantly reduced if the birth is performed by caesarean section.

In order to prevent hepatitis B infection from pregnant women who are sick with HBV or carriers of HBV, they are subject to hospitalization in specialized departments (wards) of maternity hospitals, feldsher-obstetric stations, where a strict anti-epidemic regime must be ensured.

Interruption of infection transmission routes is achieved by using individual syringes, needles, scarifiers, probes, catheters, blood transfusion systems, and other medical instruments and equipment used in procedures involving damage to the integrity of the skin and mucous membranes.

If reuse is necessary, all medical instruments and equipment must be thoroughly cleaned and sterilized after each use.

The quality of instrument washing is determined using a benzidine or amidopyrine test, which allows the presence of traces of blood to be detected. If the tests are positive, the instruments are reprocessed.

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

Strict adherence to the indications for hemotherapy is of great importance for the prevention of post-transfusion hepatitis. Transfusion of preserved blood and its components (erythrocyte mass, plasma, antithrombin, concentrates VII, VIII) is carried out only for vital indications, which should be reflected in the medical history.

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

For the prevention of hepatitis B, the following are important: transfusion of blood or its components from one ampoule to one recipient, direct transfusion from parents or from a donor tested for the presence of HBsAg immediately before blood donation, the use of autotransfusions with advance preparation of the patient's own blood before surgery, etc.

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

To prevent professional infections, all specialists must use disposable rubber gloves when in contact with blood and strictly adhere to personal hygiene rules.

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

Specific prophylaxis of hepatitis B

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

Passive immunization

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

• children born to mothers who are carriers of HBsAg or who have acute hepatitis B in the last months of pregnancy (immunoglobulin is administered immediately after birth, and then again after 1, 3 and 6 months);
• after virus-containing material has entered the body (blood or its components have been transfused from a patient with hepatitis B or an HBV carrier, accidental cuts, injections with suspected contamination of virus-containing material, etc.). In these cases, immunoglobulin is administered in the first hours after the suspected infection and after 1 month;
• in case of a long-term threat of infection (patients admitted to hemodialysis centers, patients with hemoblastoses, etc.) - 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. When administered immediately after infection, the prophylactic effect reaches 90%, within 2 days - 50-70%, and after 5 days, immunoglobulin prophylaxis is practically ineffective. With intramuscular administration of immunoglobulin, the peak concentration of anti-HBs in the blood is achieved after 2-5 days. For the fastest possible protective effect, you can resort to intravenous administration of immunoglobulin.

It is also important to consider that the period of immunoglobulin elimination is from 2 to 6 months, but a reliable protective effect is provided only in the 1st month from the moment of administration, therefore, to obtain a prolonged effect, it is necessary to re-administer it. In addition, the effect of using immunoglobulin is observed only with a low infective dose of HBV. In the case of massive infection (blood transfusion, plasma, etc.), immunoglobulin prophylaxis is ineffective.

It became obvious that the solution to the hepatitis B problem was only possible through mass immunization.

Characteristics of hepatitis B vaccines

There are two types of hepatitis B vaccines.

1. Inactivated vaccines obtained from the plasma of HBsAg carriers, containing 20 μg HBsAg (protein) in 1 dose (1 ml). These vaccines are not currently used.
2. Recombinant vaccines, for the production of which recombinant technology is used for the insertion of the hepatitis B virus gene subunit responsible for the production of HBsAg into yeast or other cells. After completion of the yeast cultivation process, the produced protein (HBsAg) is subjected to thorough purification from yeast proteins. Aluminum hydroxide is used as a sorbent, and thimerosal is used as a preservative.

A recombinant vaccine against hepatitis B has been developed in Russia and its production has been established at the Joint-Stock Company Scientific and Production Corporation "Combiotech". The development of the first domestic recombinant yeast vaccine against hepatitis B was completed in 1992 and after a full cycle of state trials conducted by the L.A. Tarasevich State Institute of Skin and Blood Diseases, it was included in the State Register of Medicines. The vaccine is available in 1 ml vials containing 20 μg of HBsAg (adult dose) and 0.5 ml containing 10 μg of HBsAg (children's dose). The preservative is 0.005% thimerosal. The shelf life of the vaccine is 3 years. The vaccine's characteristics meet WHO requirements and are not inferior to foreign analogues registered on the Russian market.

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

• hepatitis B vaccine DNA recombinant produced by the Federal State Unitary Enterprise Scientific and Production Association Virion (Tomsk);
• Regevak B produced by ZAO "Medical and Technological Holding",

In addition, several foreign vaccine preparations have been registered:

• Engerix B produced by GlaxoSmithKline (Belgium);
• Euvax B vaccine (South Korea);
• hepatitis B vaccine, recombinant HB VAX II, manufactured by Merck Sharp & Dohme (USA);
• Shanvak-V vaccine from Shanta-Biotechnologies PVTLTD (India).

In recent years, new associated vaccines have been developed and approved for use in Russia: a combined vaccine against hepatitis B, diphtheria and tetanus (bubo-M), a combined vaccine against hepatitis A and B, a combined vaccine against hepatitis B, diphtheria, tetanus and whooping cough (bubo-Kok).

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Hepatitis B Vaccination Schedules

To create strong immunity, three doses of the vaccine are required. The first two injections can be considered as initial doses, while the third serves to enhance antibody production. The administration schedule may 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, an accelerated vaccination schedule may be used, for example, according to the 0-1-2 months or 0-2-4 months schedule. In this case, an earlier formation of a protective level of antibodies is observed in a larger number of patients. When using schedules 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 with accelerated vaccination schedules. The vaccine dose is calculated based on 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 carried out according to the 0-1-6 months schedule. In some countries, vaccination is carried out only in risk groups (healthcare workers, primarily surgeons, dentists, obstetricians, blood transfusion service workers, patients undergoing 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 to administer 0.5 ml of immunoglobulin against the hepatitis B virus immediately after birth (no later than 48 hours) (not mandatory in recent years) and begin three-time immunization with the vaccine according to the 0-1-6 months schedule.

The hepatitis B vaccine is administered intramuscularly only; in adults and older children, it should be administered into the deltoid muscle; in young children and newborns, it is preferable to administer it into the anterolateral part of the thigh. Injections of the vaccine into the gluteal region are undesirable due to a decrease in the immune system.

Currently, according to the national calendar, newborns from risk groups are vaccinated according to the schedule 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 schedule (the first dose is administered at the start of vaccination, the second dose is administered 3 months after the first vaccination, and the third dose is administered 6 months after the start of immunization).

Post-vaccination immunity

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

The vaccination effectiveness index ranged from 7.8 to 18.1, but in patients in the hemodialysis departments it was only 2.4.

Based on the generalized experience of using the Engerix B vaccine in 40 countries, the WHO concluded that the seroconversion rate after 3 doses of the 0-1-2 or 0-1-6 month schedule is close to 100%. The third dose administered at 2 months, compared with the third dose administered at 6 months, ultimately results in a less significant increase in antibody titers, so the 0-1-6 month schedule can be recommended for routine vaccination, while the 0-1-2 month schedule is recommended in cases where it is necessary to quickly achieve a sufficient level of immunity. In the future, these children can achieve a more reliable level of antibodies by administering a booster dose after 12 months.

The question of the duration of post-vaccination immunity is more difficult to answer. According to most literature sources, the level of antibodies after three-dose vaccination decreases rapidly during the first 12 months after vaccination, then the decrease is slower. Most authors are inclined to believe that there is most likely no need to revaccinate patients with high seroconversion rates (above 100 IU/day). At the same time, it is suggested that the body's immunological memory is as reliable a means of protection 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 a protection level below 100 IU/l.

Vaccination reactions and complications after hepatitis B vaccination

Recombinant vaccines against hepatitis B are low-reactogenic. Only a few patients experience a reaction at the injection site (mild hyperemia, less often edema) 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 (Engerix B, etc.), local reactions (pain, hypersensitivity, itching, erythema, ecchymosis, swelling, nodule formation) occur in a total of 16.7% of those vaccinated; among general reactions, asthenia is noted in 4.2%, malaise - in 1.2, increased body temperature - in 3.2, nausea - in 1.8, diarrhea - in 1.1, headache - in 4.1%; increased sweating, chills, hypotension, Quincke's edema, decreased appetite, arthralgia, myalgia, etc. are also possible.

Similar side effects are described for the introduction of the domestic vaccine kombiotekh. All these reactions do not significantly affect health, are short-term and are most likely caused by the presence of yeast protein impurities in recombinant vaccines.

Precautions and contraindications for hepatitis B vaccination

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

Vaccination against hepatitis B should be carried out with some caution in patients with severe cardiovascular insufficiency, patients with chronic kidney, liver, and CNS diseases. However, such conditions do not serve as a contraindication to the administration of recombinant vaccines, and if we consider 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 first.

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 undergoing 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 performed if the potential benefit justifies the possible risk to the fetus.

On the combination of hepatitis B vaccination with other vaccines

The implementation of the Russian program of hepatitis B vaccination starting from the neonatal period invariably raises the question of combining the vaccine with other vaccines for each pediatrician, and first of all with the BCG vaccine. From a scientific point of view, concerns about the incompatibility of these vaccines are completely unfounded, since it is known that an increase in the level of protection when administering the BCG vaccine is achieved by forming cellular immunity of the type of post-vaccination allergy, whereas humoral immunity is formed when administering the hepatitis B vaccine.

Studies show that when the yeast recombinant vaccine Engerix B is administered in the first 24-48 hours of life and vaccinated on the 4th-7th day against tuberculosis, no adverse interdependent effects are observed. At the same time, 95.6% of children developed protective immunity against hepatitis B and there was no noticeable decrease in the level of protection against tuberculosis, which could be judged by the stable level of tuberculosis incidence after the start of mass vaccination against hepatitis B.

On the other hand, the introduction of the hepatitis B vaccine immediately after the birth of the 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 sick with hepatitis B, as well as in regions with a high level of spread of HB-virus infection. First of all, these are regions of Siberia, the Far East, the Republic of Tyva, Kalmykia, etc.

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

Children from families with an HBsAg carrier or a patient with hepatitis B are also subject to priority vaccination against hepatitis B. According to research, in families with 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 observed in orphanages and boarding schools, that is, in institutions where there is close contact and a high probability of transmitting the infection by the so-called contact route, through microtrauma, household items, etc. It is better to start vaccinating sero-negative children in such foci after a mass examination of children for hepatitis B markers. If for some reason it is impossible to determine hepatitis B markers, vaccination can be carried out without waiting for the examination results. At the same time, the negative consequences of administering the vaccine to children (and adults) with post-infection immunity or even an 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 side effects 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, determining 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 preliminary expensive laboratory testing.

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 carried out four times according to the scheme 0-1-2-6 months, while for patients on hemodialysis, the vaccine doses are doubled.

Vaccination of children against hepatitis B with oncohematological diseases

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

According to research data, during a single screening examination, hepatitis B markers are detected in 60.2% of patients with hemoblastoses, in 36.5% of patients with solid tumors, in 85.2% of patients with hemophilia and only in 6% of patients with acute intestinal infection, and in children from families kept at home - in 4.3% of cases. It would seem that patients with hemoblastoses, solid tumors and hemophilia should be vaccinated first, but it is known that under conditions of immunodeficiency, the development of immunity to the introduction 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 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 immediately after the diagnosis of cancer. Vaccination of such patients should be carried out until protective immunity appears according to the following schedule: 0-1-3-6-12 or 0-1-2-3-6-12 months.