Vaccination against rotavirus infection

Rotavirus rights - a representative of the family of RNA viruses that infect animals. The main serotypes of rotaviruses circulating in Europe are G1P (50-75%), G4P (5-50%), G3P and G2P (1-25%); in recent years, the serotype G9P (9-39%) has often become prominent. In Africa, the serotypes of R.

Rotavirus infection - the main cause of acute gastroenteritis, by the age of 5 years, it is tolerated by almost all children, usually twice. Epidemics are observed in the winter-spring period. Copious watery diarrhea, vomiting and fever leads to dehydration, requiring rehydration, often intravenously. In the world, rotavirus takes away more than 600,000 children's lives per year, mainly in developing countries.

Rotavirus, according to estimates, in the European Union annually causes 2.8 million cases (1: 7 children) of gastroenteritis with 87,000 hospitalizations (1:54 children). In the US, rotaviruses account for 31-50% of all diarrhea in children under 5 years of age, in Europe - 50-65%, and in winter their proportion increases to 80%. Appeal to the doctor for rotavirus gastroenteritis can reach 40-50 per 1000 children under 5 years of age, the appeal to emergency departments of hospitals is 15-26 per 1000, hospitalizations - 3-12 per 1000.

In Russia, even with incomplete registration, rotavirus is also a serious problem, in regions where diagnostics of rotavirus gastroenteritis is established, the incidence of children under 2 years exceeds 2500 per 100,000, and during outbreaks reaches 8,000-9,000. Among hospitalized children with diarrhea, rotavirus diseases in the season is 70-80%.

Among all the causes of nosocomial diarrhea viruses are 91-94%, and among them the specific gravity of rotaviruses, according to various sources, is 31-87%. In countries of Europe, 5-27% of all hospitalized children of early and, especially, infants are infected with rotavirus gastroenteritis. With the high contagiousness of rotavirus, a significant proportion of patients are hospitalized in general departments with a high fever, whereas diarrhea begins later. Asymptomatic carriers of the virus among hospitalized children may be 5-7%. In these conditions, even very strict hygiene measures (washing hands after contact with the patient) are not always effective.

The effectiveness of the vaccine against rotavirus infection

Rotaryx causes a seroconversion in> 80% of the vaccinated, allocation of a vaccine virus with a stool for a maximum of 2 weeks. And quickly ends (by the 30th day only 10-20% of the vaccinated virus was isolated). The protective effect is manifested even after the 1st dose (mostly type-specific), after the second dose - heterotypic.

The effectiveness of Rotaryx for 2 seasons in relation to more severe forms of rotavirus infection was 83%, of all forms - 60-70%; (88-92% for diseases caused by serotypes of Gl, G3 and G9, 72% - for serotype G2P). The incidence of severe gastroenteritis of any etiology decreased by 40%, which may indicate the inhibitory effect of the vaccine virus on the replication of other intestinal viruses. In Europe, Rotaryx showed 96-100% effectiveness in terms of requiring hospitalization cases during the first year, during the second year - 83%.

Rotarix are combined with simultaneous administration with all inactivated vaccines, including conjugated.

RotaTech causes more than 3-fold increase in antibody titer in more than 95% of vaccinated, reduces the risk of rotavirus gastroenteritis in the first year by 74%, and of severe rotavirus gastroenteritis in the 1st year by 98%, in the second - by 88%. The risk of hospitalization decreased by 96%, emergency treatment by 94%, to the doctor - by 86%, and the number of days of incapacity for work - by 87%. The RotaTech effect is manifested in relation to serotypes G1 (95%), G3 (93%), G4 (89%) and G9 (100%). The RotaTech vaccine is effective in premature babies who are in a stable state. Vaccination is also possible for children whose families have immunodeficiency viruses, including AIDS.

The preliminary result of the massive use of this vaccine in the US showed that in 2007-2008, the activity of rotavirus infection began at 2-4 months. Later than before the vaccination (November - end of February), and the peak incidence (for the isolation of rotavirus) fell in April instead of March and was significantly more flat (17.8% instead of 30.6-45.5% in the pre-vaccination years). Isolation of rotavirus in children under 3 years with diarrhea decreased from 54 to 6%.

Vaccines against rotavirus infection

The difficulty in creating a vaccine against rotavirus infection, the pathogens of which have many serotypes, was overcome by observing that 2 of the rotavirus diseases carried by a child - usually at an early age - make it immune to infection with rotaviruses of any serotype. Consequently, a two-fold administration of a vaccine, even prepared from rotavirus of a single serotype, will have an immunizing effect against any rotavirus.

To create vaccines, the ability of rotaviruses to recombine genetic material has been used. The first experience of using the vaccine, created on the basis of rotavirus of rhesus monkeys, was unsuccessful: in the USA in 1998 the mass vaccination of children with such a vaccine was started - Rotashild. However, the use of this vaccine was accompanied by the appearance of cases of intestinal invagination with a frequency of about 1:10 000 doses (only about 100 cases), which naturally led to its termination. This unfortunate experience has shown the importance of careful monitoring of the frequency of intussusception when using any rotavirus vaccine.

In Russia, two vaccines are being registered.

Vaccine Rotarix, licensed in more than 125 countries around the world, including in the US. Was tested in Russia, in 2009 it is expected to be registered in Russia. The RotaTech vaccine in the United States was introduced into the Calendar in February 2006, used since 2007 in Europe, filed for registration in Russia.

Rotavirus vaccines registered in Russia

Vaccine	Composition
Rotaryx - oral live monovalent - GlaxoSmithKline, England	A strain of RIX4414, a serotype of GlPal, is prepared on the basis of an ateniated human rotavirus; is issued as a dry white powder and a solvent (cloudy liquid with white precipitate), 1 dose (1 ml) contains not less than 10 6.0 CCID50 rotavirus. It is entered twice. Store at 2-8 ° for 2 years.
RotaTek® - oral live 5-valent reassortant vaccine - Merck Sharp and Dome, Netherlands	Contains 5 reassortant viruses based on human and bovine (non-pathogenic to humans) strains. 4 reassortants are carried on the outer shell surface proteins VP7 serotypes Gl, G2, G3, G4 human strains of rotavirus and VP4 serotype P7 of the bovine strain, 5 reassortant - protein P1 A from human and protein G6 from bovine parent strains. Entered 3 times.

Based on the evidence, a group of European experts - infectious disease specialists and gastroenterologists recommend:

1. Mass vaccination of healthy children in all countries of Europe using the available vaccines Rotarix and RotaTech
2. Both vaccines can be included in the National Vaccination Schedules for administration at the same time or at different times with other vaccines 
3. It is necessary to introduce permanent post-licensing monitoring for serious undesirable phenomena. 
4. Vaccination of prematurity, children with hypotrophy, infected with HIV can be carried out according to the same scheme as healthy ones by the decision of the attending physician.

The timing, dose and method of administering the vaccine against rotavirus infection

Given the increased intussusception in children over 6 months of age and the negative experience with the Rotasild vaccine, new vaccines are administered at the age of 6 weeks. With an interval of 4-6 weeks. The second dose of Rotarix should be administered before the age of 16 weeks, but in any case not later than 24 weeks. The first dose of RotaTek is administered between 6 and 12 weeks, completing the vaccination by 32 weeks. (at a later date, vaccination was not investigated and is not recommended).

Reactogenicity and contraindications to the vaccine against rotavirus infection

The reactogenicity of both vaccines is low, the frequency of the temperature reaction, emesis, irritability, diarrhea, loss of appetite among the vaccinated (both mono and together with other calendar vaccines) does not differ significantly from that for the placebo group. The incidence of serious adverse events in children receiving RotaTech was less than in the placebo group.

It is very important that the incidence of intussusception in vaccinated patients not only does not increase, but even decreases: the OR for Rotaryx was 0.5 after the 1st dose and 0.99 after the 2nd dose, for 10 000 vaccinated it decreases by 0.32 cases. The same results were given by the RotaTech vaccine: there were 12 cases of intussusception with 68 cases of vaccination, and 18 cases in a similar placebo group. The protective effect of vaccination against intussusception may be due to the suppression of replicating viruses associated with intussusception with vaccine, in particular adenoviruses.

RotaTech and Rotaryx are contraindicated in children with hypersensitivity to vaccine components or responding to a previous dose, children with developmental disorders of the gastrointestinal tract who have undergone intussusception, with immunodeficiencies. Vaccination is delayed in children with severe illness, intestinal disorders, vomiting; an easy disease is not a contraindication.