Vaccination against rotavirus infection

Human rotavirus is a member of the RNA virus family that infects animals. The main rotavirus serotypes circulating in Europe are G1P (50-75%), G4P (5-50%), G3P and G2P (1-25%); in recent years, the G9P serotype (9-39%) has become increasingly common. In Africa, the most common serotypes are P.

Rotavirus infection is the leading cause of acute gastroenteritis; by the age of 5, almost all children have had it, usually twice. Epidemics occur in the winter and spring. Severe watery diarrhea, vomiting, and fever lead to dehydration, requiring rehydration, often intravenously. Rotavirus kills more than 600,000 children a year worldwide, mostly in developing countries.

Rotavirus is estimated to cause 2.8 million cases (1:7 children) of gastroenteritis with 87,000 hospitalizations (1:54 children) in the EU each year. In the USA, rotaviruses cause 31-50% of all diarrhea in children under 5 years of age, in Europe - 50-65%, and in winter their share increases to 80%. The number of visits to a doctor for rotavirus gastroenteritis can reach 40-50 per 1000 children under 5 years of age, the number of visits to emergency departments of hospitals - 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 well established, the incidence of children under 2 years of age exceeds 2,500 per 100,000, and during outbreaks reaches 8,000 - 9,000. Among hospitalized children with diarrhea, rotavirus diseases during the season account for 70-80%.

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

Efficacy of the rotavirus vaccine

Rotarix causes seroconversion in >80% of vaccinated persons, excretion of vaccine virus with stool is maximal on the 2nd week and ends quickly (by the 30th day only 10-20% of vaccinated persons excreted the virus). The protective effect is already evident after the 1st dose (mostly type-specific), after the 2nd dose - heterotypic.

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

Rotarix is compatible with simultaneous administration with all inactivated vaccines, including conjugate vaccines.

RotaTeq causes a more than 3-fold increase in antibody titers in more than 95% of those vaccinated, reduces the risk of rotavirus gastroenteritis in the first year by 74%, and severe rotavirus gastroenteritis in the first year by 98%, in the second - by 88%. The risk of hospitalization decreased by 96%, visits to emergency departments - by 94%, visits to a doctor - by 86%, the number of days of incapacity for work - by 87%. The effect of RotaTeq is manifested in relation to serotypes G1 (95%), G3 (93%), G4 (89%) and G9 (100%). The RotaTeq vaccine is effective in premature infants in a stable condition. Vaccination is also possible for children in whose families there are patients with immunodeficiency, including AIDS.

Preliminary results of mass use of this vaccine in the USA showed that in 2007-2008, rotavirus infection activity began 2-4 months later than before vaccination (November - end of February), and the peak of morbidity (by rotavirus isolation) occurred in April instead of March and was significantly flatter (17.8% instead of 30.6-45.5% in pre-vaccination years). Rotavirus isolation in children under 3 years of age with diarrhea decreased from 54 to 6%.

Vaccines against rotavirus infection

The difficulty in creating a vaccine against rotavirus infection, the causative agents of which have many serotypes, was overcome by the observation that two rotavirus infections suffered by a child - usually at an early age - make him immune to infection with rotaviruses of any serotype. Consequently, two doses of the vaccine, even prepared from a single serotype of rotavirus, will have an immunizing effect against any rotavirus.

The ability of rotaviruses to recombine genetic material was used to create vaccines. The first experience with a vaccine created on the basis of the rotavirus of rhesus macaques was unsuccessful: in the USA in 1998, mass vaccination of children with such a vaccine - Rotashield - was launched. However, the use of this vaccine was accompanied by the occurrence of cases of intestinal intussusception with a frequency of about 1:10,000 doses (a total of about 100 cases), which, naturally, forced its use to be stopped. This unsuccessful experience showed the importance of careful monitoring of the frequency of intussusception when using any rotavirus vaccine.

Two vaccines are undergoing registration in Russia.

The Rotarix vaccine, licensed in more than 125 countries worldwide, including the USA, has been tested in Russia, and is expected to be registered in Russia in 2009. The RotaTeq vaccine was introduced into the Calendar in the USA in February 2006, has been used in Europe since 2007, and has been submitted for registration in Russia.

Rotavirus vaccines registered in Russia

Vaccine	Compound
Rotarix - oral live monovalent - GlaxoSmithKline, England	Prepared on the basis of attenuated human rotavirus strain RIX4414 - serotype GlPal); available as a dry white powder and solvent (turbid liquid with white sediment), 1 dose (1 ml) contains at least 10 6.0 CCID50 rotavirus. Administered twice. Store at 2-8° for 2 years.
RotaTeq® - oral live 5-valent reassortant vaccine - Merck Sharp & Dohme, The Netherlands	Contains 5 reassortant viruses based on human and bovine (non-pathogenic for humans) strains. 4 reassortants carry on the outer shell the surface proteins VP7 of serotypes Gl, G2, G3, G4 of human rotavirus strains and VP4 of serotype P7 of the bovine strain, the 5th reassortant - protein P1 A from the human and protein G6 from the bovine parent strains. It is administered 3 times.

Based on evidence, a group of European infectious disease and gastroenterology experts recommends:

1. Carrying out mass vaccination of healthy children in all European countries using the existing Rotarix and RotaTeq vaccines
2. Both vaccines can be included in the National Immunization Schedules for administration at the same time or at different times with other vaccines.
3. Continuous post-licensure monitoring for serious adverse events should be introduced.
4. Vaccination of premature babies, children with malnutrition, and HIV-infected children can be carried out according to the same schedule as for healthy children, at the discretion of the attending physician.

Timing, dose and method of administration of the rotavirus vaccine

Given the increased incidence of intussusception in children over 6 months of age and the negative experience with the Rotashield vaccine, new vaccines are administered from the age of 6 weeks at intervals of 4-6 weeks. The second dose of Rotarix should preferably be administered before the age of 16 weeks, but in any case no later than 24 weeks. The first dose of RotaTeq is administered between 6 and 12 weeks, completing vaccination by 32 weeks (vaccination at later dates has not been studied and is not recommended).

Reactogenicity and contraindications to the administration of the rotavirus vaccine

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

It is very important that the frequency of intussusceptions in vaccinated people not only does not increase, but even decreases: the OR for Rotarix was 0.5 after the 1st dose and 0.99 after the 2nd, per 10,000 vaccinated people it decreases by 0.32 cases. The same results were obtained with the RotaTeq vaccine: per 68 thousand vaccinated people there were 12 cases of intussusception, and in a similarly sized placebo group - 18 cases. The protective effect of vaccination against intussusception may be associated with the suppression by the vaccine of the replication of viruses associated with intussusception, in particular, adenoviruses.

RotaTeq and Rotarix are contraindicated in children with hypersensitivity to vaccine components or who have reacted to a previous dose, children with gastrointestinal malformations, those who have had intussusception, and those with immunodeficiencies. Vaccination is postponed in children with severe illness, intestinal disorders, vomiting; mild illness is not a contraindication.