Hepatitis B vaccination

The incidence of acute hepatitis B in Russia, which had been increasing until the beginning of this century, has decreased from 42 per 100,000 inhabitants in 2001 to 5.26 in 2007. An even sharper decrease in incidence was observed in childhood.

The rapid decline in incidence is a consequence of the high coverage of hepatitis B vaccinations among newborns and adolescents. However, the high incidence in the past will make itself felt for a long time to come: the number of newly diagnosed cases of chronic hepatitis is much higher than the number of acute hepatitis B: in 2004 it was about 75,000 with 15,000 acute cases, in 2006 the corresponding figures were 20,000 and 10,000. To this should be added 68,000 newly diagnosed carriers of the hepatitis B virus. In 2006, 417 cases of chronic hepatitis and 1,700 HBsAg carriers were detected among children.

The total number of hepatitis B carriers in Russia exceeds 3 million people. About 90% of newborns from mothers who are HBeAg carriers are infected during childbirth; if the mother is only HBsAg carrier, the risk of vertical transmission of the virus to the newborn is lower, but they all have a high risk of infection during breastfeeding and close contact with the mother. In newborns, hepatitis B becomes chronic in 90% of cases, in 50% of cases when infected in the first year of life, and in 5-10% of cases in adults. Therefore, the importance of preventing vertical transmission of hepatitis B by vaccinating children against hepatitis B on the first day of life is obvious. This is in line with the WHO strategy.

Vaccination against hepatitis B on the first day of life by 2005 was introduced in 80% of countries, including those with low endemicity of HBV infection (USA, Switzerland, Italy, Spain, Portugal). Relying on the results of testing pregnant women for HBsAg and vaccinating only children from mothers who are carriers is unreliable: as studies conducted in Russia have shown, about 40% of carriers were not detected using routine testing (on a national scale, this is 8-10 thousand children) - and this is with a very high quality of testing (only 0.5% errors). Therefore, it is entirely legitimate to maintain the first hepatitis B vaccination in the first 12 hours of a child’s life, as stipulated by the 2007 National Calendar. The same measure was introduced in the United States in 2006, since about 2,000 children are born in the United States every year from mothers who are HBsAg carriers and who were not identified in the prenatal period.

Objections to vaccination on the first day of life were related to the complexity of its organization, as well as to the possible decrease in coverage with other vaccinations. Studies, on the contrary, have shown that vaccination against hepatitis B at birth increases the rate of timely completion of both the course of this vaccination and other calendar vaccines. The interaction of BCG and HBV administered in the neonatal period was not confirmed by the size of the Mantoux test, the size of the vaccination scar, the level of antibodies to HBsAg, or the number of complications. Cases of bleeding from the site of administration of the 2nd dose of viral hepatitis B in one of the regions were caused by hemorrhagic disease of newborns who did not receive vitamin K prophylactically.

Vaccination against hepatitis B on the first day of a child’s life does not increase the injection load, since according to the 0-3-6 months schedule, it is possible to use combination vaccines.

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Objectives of Hepatitis B Vaccination Programs

The WHO European Hepatitis B Office's goal of "90% coverage of hepatitis B vaccines in target populations by 2005 or earlier" has been achieved in Russia. The reduction in incidence through mass vaccination is impressive. The experience of Taiwan and South Korea shows that mass vaccination of newborns dramatically reduces the incidence of liver cancer in children. Mass vaccination of all persons up to the age of 55 will create conditions for stopping the transmission of the infection, the reservoir of which is a large number of HBsAg carriers and patients with chronic hepatitis B.

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Hepatitis B Vaccination: Vaccine Preparations

Genetically engineered vaccines are inactivated and contain only vaccine protein. They are sorbed on aluminum hydroxide, the preservative thimerosal is not used in a number of vaccines, and newborns should be vaccinated with them. Combined vaccines HBV+DPT are preferable at the age of 3 and 6 months. The HBV+ADS-M vaccine in adults will allow combining vaccination against hepatitis B and routine revaccination against diphtheria. Vaccines are stored at 2-8°C.

Hepatitis B vaccines are highly immunogenic, with protective titer antibodies formed in 95-99% of those vaccinated, with protection lasting 8 years or more. Premature infants weighing less than 2 kg may have a weakened immune response, and are vaccinated starting at 2 months of age. If the mother is a carrier of the virus, the vaccination is administered on the first day of life, with simultaneous administration of 100 IU of specific immunoglobulin. Immunoglobulin is also used for post-exposure prophylaxis. Seroconversion to the hepatitis A virus with Twinrix reaches 89% 1 month after the first dose and 100% after the second, and to the hepatitis B virus - 93.4% after 2 months and 97.7% after 6 months.

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Hepatitis B vaccination methods and schedules

All vaccines are intended for both children and adults, including risk groups, and are administered in age-related doses intramuscularly. All vaccines are interchangeable. Since 2008, 1-year-old children have been vaccinated according to the 0-3-6 months schedule, while risk group children have been vaccinated according to the 0-1-2-12 months schedule. Unvaccinated children, adolescents, and adults are vaccinated according to the 0-1-6 schedule. Emergency vaccination (for example, before surgery with massive blood transfusion) with Engerix B is carried out according to the 0-7-21 day schedule with revaccination after 12 months. The interval before the second dose may be extended to 8-12 weeks, but in risk groups it is better to limit it to 4-6 weeks. The timing of the third dose may vary even more - up to 12-18 months after the first dose. When using combination vaccines, the 0-2-6 month schedules are justified. and 0-3-6 months, they are used in Spain, USA, Kazakhstan.

Hepatitis B monovalent vaccines registered in Russia

Vaccine	Contents, preservative	Dosage
Recombinant yeast ZAO Combiotech, Russia	20 mcg in 1 ml. Available with or without thimerosal.	Persons over 18 years of age are administered 20 mcg (1 ml), under 18 years of age - 10 mcg (0.5 ml). Persons on hemodialysis are administered a double adult dose - 2.0 ml.
Regevak, ZAO MTX, Russia	20 mcg per 1 ml, preservative - merthiolate 0.005%.
Biovac-V, Wockhard Ltd.,	20 mcg per 1 ml, preservative - merthiolate 0.025 mg
Eberbiovac NV, Center for Genetic Engineering, Cuba	20 mcg in 1 ml, contains 0.005% thimerosal
"Engerix V" Russia; SmithKline Beecham-Biomed,	Particles (20 nm) coated with a lipid matrix - 20	The same, but from 16 years old
Hep B vaccine recombinant (rDNA) Serum Institute Ltd, India	20 mcg per 1 ml, preservative - merthiolate	It is administered to persons over 10 years of age at 20 mcg (1 ml), under 10 years of age - 10 mcg (0.5 ml)
Shanvak-V, Shanta Biotechnics PTV Ltd, India	20 mcg per 1 ml, preservative - merthiolate 0.005%
Euvax B, LG Life Sciences, South Korea under the control of Sanofi Pasteur	20 mcg in 1.0 ml, thimerosal not more than 0.0046%	For persons over 16 years of age, 20 mcg (1.0 ml) is administered, children's dose is 10 mcg (0.5 ml)
N-B-Wax® II, Merck Sharp Dome, The Netherlands	5 mcg in 0.5 ml, 10 mcg/ml - 1 and 3 ml, 40 mcg/ml - 1.0 ml (for people on hemodialysis). Without preservative	Adults 10 mcg, adolescents 11-19 years old - 5 mcg, children under 10 years old - 2.5 mcg. Children of mothers-carriers - 5 mcg

HEP-A+B-in-VAC is used for simultaneous vaccination against hepatitis A and B for children over 3 years of age and adults according to the 0-1-6 months schedule, Twinrix - from the age of 1 year according to the same schedule or urgently (0-7-21 days + quarter dose after 1 year).

In a number of countries, children born to HBsAg-positive mothers are recommended to receive (at a different site) a specific immunoglobulin at a dose of 100 IU simultaneously with vaccination, which increases the effectiveness by 1-2%; this scheme should be kept in mind for children whose mothers have HBeAg in addition to HBsAg.

Revaccination. After vaccination, antibodies can persist for up to 20 years and protection is also provided by immunological memory, even in the absence of antibodies. Therefore, WHO does not recommend revaccination, at least for 10-15 years, it is indicated only for health workers (every 7 years) and people at risk (hemodialysis, immunodeficiency).

Serological screening before vaccination is not required, since the introduction of the vaccine to HBsAg carriers is not dangerous, and for individuals with antibodies to the hepatitis B virus, vaccination can act as a booster. Testing for the presence of antibodies is justified in risk groups (immunodeficiency, children from mothers-carriers) 1 and 3 months after the last dose; if the anti-HBs level is below 10 mIU/ml, another dose of the vaccine is administered.

Combination vaccines registered in Russia

Vaccine	Contents, preservative	Dosage
Bubo-M - diphtheria-tetanus-hepatitis B, ZAO Kombiotekh, Russia	In 1 dose (0.5 ml) 10 mcg HBsAg, 5 LF diphtheria and 5 EU tetanus toxoids, preservative - 2-phenoxyethanol, 0.005% thimerosal	Used for vaccination of persons over 6 years of age
Bubo-Kok - pertussis-diphtheria-tetanus-hepatitis B, ZAO Kombiotekh, Russia	In 1 dose (0.5 ml) 5 mcg HBsAg, 10 billion whooping cough microbes, 15 LF diphtheria and 5 EU tetanus toxoids, preservative - merthiolate 50 mcg	Used in children under 5 years of age
Twinrix - Hepatitis A and B vaccine, Gpaxo SmithKline, England	20 mcg HBsAg +720 UHV Ag in 1.0 ml (adult vaccine) preservative - 2-phenoxyethanol, formaldehyde less than 0.015%	Persons over 16 years of age are given an adult dose (1.0 ml), and children from 1 to 15 years of age are given a child dose (0.5 ml) of the vaccine.
Hep-A+B-in-VAC - hepatitis A+B divaccine, Russia	1 ml contains 80 units of ELISA AG HAV and 20 μg HesAg (in the registration phase)	1.0 ml is administered to persons over 17 years of age, 0.5 ml - to children 3-17 years of age

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Vaccination reactions and complications

Hepatitis B vaccines are low reactogenic, some vaccinated people (up to 17%) may develop hyperemia and induration at the injection site, short-term deterioration in health; an increase in temperature is noted in 1-6%. No differences in the frequency of reactions, intercurrent morbidity and physical development were found when DPT + OPV + HBV and only DPT + OPV were administered in the first year of life.

Since 1980, more than 1 billion doses of hepatitis B vaccines have been administered, with isolated cases of anaphylactic shock (1:600,000), urticaria (1:100,000), rash (1:30,000), joint pain, myalgia, and erythema nodosum reported. An anaphylactoid reaction was occasionally observed in a child with yeast intolerance (bread allergy). A case of mesangial-proliferative IgA glomerulonephritis with HBsAg deposition in the glomerulus and tubules, which began with hematuria 2 weeks after the 2nd dose of HBV, has been described.

The publications that have been published on the connection between hepatitis B immunoprophylaxis and the development of multiple sclerosis and other demyelinating diseases have been rejected after repeated careful testing; most likely, the hypothesis of a coincidence in time of the onset of multiple sclerosis and vaccination.

Bubo-Kok is comparable in reactogenicity to DPT, Twinrix is also low reactogenic. The introduction of specific immunoglobulin may cause redness at the injection site and a temperature of up to 37.5.

Contraindications to hepatitis B vaccination

Increased sensitivity to yeast and other components of the drug, decompensated forms of cardiovascular and pulmonary diseases. Persons with acute infectious diseases are vaccinated after recovery.

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Post-exposure prophylaxis of hepatitis B

Hepatitis B vaccination prevents infection when administered early after exposure. Unvaccinated healthcare workers and other individuals who have had or may have had contact with the blood or secretions of a patient, carrier, or person of unknown status (always considered an HBsAg carrier) should be vaccinated on the first day, preferably with the simultaneous administration of specific immunoglobulin (no later than 48 hours) into different parts of the body at a dose of 0.12 ml (at least 6 IU) per 1 kg of body weight. The vaccination schedule is 0-1-2-6 months, preferably with monitoring of hepatitis markers (not earlier than 3-4 months after the administration of immunoglobulin). In a previously vaccinated healthcare worker, the antibody level should be immediately determined upon exposure; with titers of 10 mIU/ml and higher, prophylaxis is not carried out; if none, 1 dose of the vaccine and immunoglobulin is administered (or 2 doses of immunoglobulin at an interval of 1 month).

The sexual partner of a patient with acute hepatitis B, if he has no markers of hepatitis, should receive 1 dose of specific immunoglobulin (its effect is unlikely to last more than 2 weeks) and immediately begin vaccination. The effectiveness of this measure is estimated at 75%.

Partially vaccinated infants from family contacts with acute hepatitis B should continue the vaccination schedule. Unvaccinated persons should be given 100 IU of specific immunoglobulin and the vaccine. The remaining contacts are vaccinated, but those who have had contact with the patient's blood are recommended the same measures as health care workers.

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Vaccination against hepatitis B in persons with chronic and oncohematological diseases

People with chronic diseases can be vaccinated during the period of remission; there is experience of vaccinating children with chronic glomerulonephritis, chronic bronchopulmonary diseases, etc. against hepatitis B. A special indication is chronic hepatitis C.

In oncohematological diseases requiring repeated blood transfusions, the introduction of the hepatitis B vaccine in the acute period does not cause the required immune response, although repeated vaccination against hepatitis B ultimately leads to seroconversion in more than 60% of cases. Therefore, it is necessary to start with passive protection with specific immunoglobulin, vaccinating in the period of remission.

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