Measles, mumps and rubella vaccination

Measles, mumps and rubella - these 3 infections have both similar epidemiology in many ways and vaccine characteristics that allow them to be combined, which justifies their joint presentation.

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Measles Elimination Program

Measles elimination is understood as achieving a state where there is no transmission of the infection and no secondary spread from an imported case. The strategy of the first stage of measles elimination envisaged a decrease in the proportion of people susceptible to measles to low levels by 2005 and maintaining this level until 2007. In Russia, the coverage of the first dose exceeded 95% in 2000, and the second - only in 2003. In 2005, only 454 cases of measles were registered (0.3 per 100,000 population); out of 327 measles foci, 282 did not spread, and in 45 foci with spread there were 172 cases. In 2006, an increase in the incidence was noted (1018 cases - 0.71 per 100,000). in 2007 - its decrease (163 cases - 0.11 per 100,000, of which only 33 were in children). In the second stage, EURO/WHO expects that "by 2010 or earlier, the incidence of measles in the region should not exceed 1 case per 1 million population."

The importance of full vaccination coverage in maintaining the elimination status is evident from the experience of the United States, where in 2008 there were 131 cases of measles (as of the end of July), of which only 8 were non-residents. Of the 95 unvaccinated cases over 1 year of age, 63 were not vaccinated for "philosophical" and religious reasons - more often in states with more liberal approaches to exemptions from vaccination. The preservation of a layer of the adult population susceptible to infection justifies the inclusion of a "clean-up" in the Russian Calendar - vaccination of all persons under 35 who have received less than 2 vaccinations.

Currently, the role of laboratory verification of suspected measles cases, the organization of serological examination of patients with all exanthematous diseases (the expected number of such cases is 2 per 100 thousand of the population) and control over the implementation of anti-epidemic measures in outbreaks is increasing.

Genotyping of "wild" measles virus strains has shown that in Russia, mainly type D measles viruses circulate: Turkish (detected in Kazakhstan, Uzbekistan) and Ukrainian subtypes (detected in Belarus and Azerbaijan). In the Far East, there are cases caused by the Chinese type H1 virus. In Europe, the incidence rate is decreasing, but there are still many cases in a number of CIS countries (except Belarus).

Epidemic mumps

This infection, considered mild, can cause meningitis, pancreatitis, orchitis and is believed to be responsible for 1/4 of all cases of male infertility.

In Russia, due to intensified vaccination efforts, the incidence of epidemic mumps has been declining in recent years: from 98.9 per 100,000 children in 1998 to 14 in 2001 > 2.12 in 2005 and 1.31 in 2007. As with measles, a significant proportion of all mumps cases occur in individuals over 15 years of age (39% in 2007), indicating that there remains a significant pool of susceptible individuals who have received fewer than 2 vaccinations. To overcome the shift in incidence to adolescence (with a more severe course of infection), it is important to vaccinate all children and adolescents under 15 years of age who have been vaccinated fewer than 2 times. It is logical to use a measles-mumps divaccine when "cleaning up" measles in people under 35, since people who have not been vaccinated against measles have most likely not been vaccinated against mumps either. This would help achieve the WHO goal of reducing mumps incidence to 1 or less per 100,000 population by 2010 or earlier. Mumps was eliminated in Finland in 1999, where a two-dose vaccination with a trivacine had been administered since 1983. This has prevented up to a thousand cases of meningitis and orchitis annually, while the increase in type 1 diabetes in children aged 5-9 has stopped, which can also be linked to vaccination.

Intensifying the fight against rubella

Rubella in children is usually mild, but it is the leading cause of encephalitis. Rubella is less contagious than measles, but a patient with rubella excretes the virus for 7 days before and 7-10 days after the rash appears, as well as with asymptomatic rubella (25-50% of the total number of patients), which determines the difficulties of combating it. Children with congenital rubella can excrete the virus for up to 1-2 years. Rubella outbreaks occur when the proportion of susceptible individuals in the population is >15%.

Congenital rubella syndrome - CRS - occurs when the disease occurs in the first trimester of pregnancy: in this case, about 3/4 of children are born with congenital defects of the heart, central nervous system, and sensory organs. The scale of the problem is illustrated by figures from the USA: in 1960-1964, more than 50,000 pregnant women fell ill with rubella (half asymptomatic), 10,000 of them had miscarriages and stillbirths, more than 20,000 children were born with congenital rubella; in 2000, thanks to vaccination, only 4 cases of congenital rubella were registered, 3 of them in unvaccinated immigrants. In Russia, the accuracy of recording congenital rubella is low (in 2003, there were only 3 cases of congenital rubella), but according to data from a number of regions, the frequency of congenital rubella syndrome is 3.5 per 1000 live births (with 16.5% of susceptible pregnant women), causing 15% of all congenital malformations; rubella accounts for 27-35% of intrauterine pathology.

In 1998, the WHO Regional Committee for Europe adopted as one of its goals: “by 2010 or earlier, the incidence of rubella in the Region should not exceed 1 case per 1 million population.”

In Russia, which began mass vaccination only in 2002-2003, the very high incidence of rubella (450,000-575,000 cases per year) has begun to decline: in 2005 there were 144,745 cases of rubella (100.12 per 100,000 population), in 2006 - 133,204 (92.62), in 2007 - 30,934 (21.61). Research conducted in recent years has shown that only 50-65% of girls aged 12-15 have antibodies to rubella, which urgently raises the issue of the need for its active prevention. The risk of the disease is especially high for medical workers, medical students, employees of preschool institutions, and teachers.

Rubella was eliminated in Finland in 1999 with two MMR® II vaccinations, preventing up to 50 cases of rubella annually. The incidence of encephalitis in children was reduced by a third.

In addition to the 2-fold vaccination, the new Russian Calendar provides for a "clean-up" - vaccination of all unvaccinated (and having only 1 vaccination) children and adolescents under 18 and women aged 18-25 who have not had rubella, which will sharply reduce the incidence of rubella and eliminate congenital rubella. Only those with serological confirmation of the diagnosis should be considered as having had rubella, since the term "rubella" is often used to refer to different diseases.

Measles, mumps and rubella vaccines registered in Russia

Vaccines	Vaccine composition - content in 1 dose
JVV - measles culture live vaccine, - Microgen, Russia	>1000 TCID50 virus strain L16. Contains gentamicin sulfate (up to 10 U/dose) and traces of bovine serum.
Rueax - measles, sanofi pasteur, France	1000 TCID50 attenuated measles virus.
Mumps - Mumps Microgen Russia	>20,000 TCID50 of the L-3 strain virus, up to 25 μg of gentamicin sulfate and traces of bovine serum
Rubella - Institute of Immunology INK, Croatia	>1,000 TCID50 of the Wistar RA 27/3 strain virus, no more than 0.25 μg of neomycin sulfate.
Rubella, Serum Institute, India	>1,000 TCID50 of the virus strain RA Wistar 27/3.
Rudivax - rubella sanofi pasteur, France	>1,000 TCID50 of the Wistar RA 27/3M strain virus (author's strain of S.A. Plotkin), traces of neomycin
Mumps-measles live dry divaccine, Microgen, Russia	20,000 TCID50 of L-3 virus and 1,000 TCID50 of L-16 virus, gentamicin sulfate up to 25 mcg, traces of bovine serum
Measles, Mumps, Rubella - Serum Institute, India	1000 TCID50 of the Edmonton-Zagreb strain and rubella strain Wistar RA 27/3 viruses, as well as 5000 TCID50 of the Leningrad-Zagreb strain of mumps.
M-M-R® P - measles, mumps, rubella - Merck, Sharp, Dohme, USA	>10 TCID50 of measles virus strain Edmonston and rubella virus strain Wistar RA 27/3, as well as 2-2 10 TCID50 of mumps virus strain Jeryl Lynn
Priorix - measles, mumps, rubella GlaxoSmithKline, Belgium	>10 TCID50 measles virus strain Schwarz, rubella virus strain Wistar RA 27/3, and 10 3 ' 7 TCID50 mumps virus strain RJT 43/85 (derived from Jeryl Lynn), up to 25 μg neomycin sulfate.

Characteristics of vaccines

For the purpose of active prevention of measles, mumps and rubella, lyophilized live attenuated vaccines are used, including combined ones. Domestic measles and mumps vaccine strains are cultured on fibroblasts of Japanese quail embryos, foreign ones - chicken embryos, rubella - on diploid cells. Vaccines are produced with an attached solvent (1 dose 0.5 ml), they are stored at a temperature of 2-8 ° or in a freezer, the solvent is stored at a temperature of 2-25 °, freezing of the solvent is not allowed.

Normal human immunoglobulin is used for passive measles prophylaxis. It does not contain HBsAg, nor does it contain antibodies to HIV and HCV.

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Timing and methods of administration of measles, mumps and rubella vaccines

All vaccines are administered in a volume of 0.5 ml subcutaneously under the shoulder blade or in the outer area of the shoulder, monovalent vaccines are administered simultaneously in different parts of the body; the use of di- and trivalent vaccines reduces the number of injections. Since vaccine viruses are inactivated by ether, alcohol and detergents, it is necessary to prevent contact of the preparation with these substances, allowing them to dry before injection.

In 116 countries with high incidence of measles, vaccination is carried out at the age of 9 and even 6 months to protect infants, who are particularly susceptible to the disease. Many children may not develop immunity due to neutralization of the vaccine virus by maternal antibodies, so children are re-vaccinated in the 2nd year.

Since the 2nd vaccination against these infections, strictly speaking, is not a revaccination, but is intended to protect children who have not seroconverted after the 1st vaccination, in principle, the interval between 2 vaccinations can be any, exceeding 1 month. although, of course, during these periods there is a high probability that the factor that reduced the immune response will not cease to act during these periods. Therefore, the 2nd vaccination before school should be given to all children, even if the 1st vaccination was given at the age of 2-5 years; practically, as indicated in SP 3.1.2. 1176-02, the interval between 2 vaccinations should be at least 6 months. In different countries, the 2nd vaccination is given at the age of 3-12 years.

When carrying out a "clean-up" vaccination, it makes perfect sense to re-vaccinate all children who received the first vaccination at age 6 (mainly in 2002-2006), as well as girls vaccinated during these years at age 13. When vaccinating teenagers against rubella with a trivacine, schoolchildren vaccinated twice against measles will receive a third dose of measles and mumps vaccines; this should not be confusing, since in those vaccinated it is immediately neutralized by antibodies.

Compatibility

In case of violation of the vaccination schedule, simultaneous vaccination with live vaccines should be carried out with any other vaccine, the administration of which is indicated at the time, including DPT, ADS or HBV. Children vaccinated with a live vaccine can be re-vaccinated with another mono- or combined vaccine and vice versa. If it is necessary to perform a tuberculin test, it should be performed before vaccination against measles (in extreme cases, simultaneously with it) or 6 weeks after it, since the measles (and possibly mumps) vaccination process can cause a temporary decrease in sensitivity to tuberculin, which will give a false-negative result.

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Effectiveness of the measles, mumps and rubella vaccine

The protective titer of measles antibodies is determined in 95-98% of those vaccinated already from the beginning of the 2nd week, which allows the vaccine to be administered to contacts (up to 72 hours). According to the most long-term observations, immunity to measles lasts for more than 25 years, and only in a very small number of those vaccinated can it fade.

Immunity to mumps after successful vaccination is long lasting, more than 10 years in most people, possibly for life. A recent outbreak of mumps in England has made it possible to clarify the effectiveness of vaccinations: in children who received 1 dose, it was 96% at 2 years of age, decreasing to 66% at 11-12 years; in those who received 2 vaccinations, the effectiveness at 5-6 years was 99%, decreasing to 85% by 11-12 years. The use of mumps vaccination in contacts is less reliable (70%) than in the case of measles.

Specific immunity to rubella develops later - after 15-20 days, which does not allow it to be administered by contact; the seroconversion rate is almost 100% and lasts for more than 20 years (Rudivax - 21 years). Re-administration of live vaccines is carried out to immunize individuals who have not given an immune response to the first vaccination.

With the introduction of combination vaccines (measles-mumps divaccine, MM-RII and Priorix), antibodies to the measles virus were detected in 95-98%, to the mumps virus in 96% and to the rubella virus in 99% of those vaccinated. With the help of MMR® II in the USA, the incidence of measles decreased by 99.94% compared to the peak and the transmission of measles was interrupted for 16 weeks, and in Finland, by the end of the 12-year period, the elimination of all 3 infections was achieved.

Vaccination reactions and complications

All live vaccines - both combined and monovaccines - are slightly reactogenic. Measles vaccination is accompanied by a specific reaction in 5-15% of children from the 5-6th to the 15th day: temperature (rarely up to 39°), catarrh ( cough, slight conjunctivitis, runny nose ), in 2-5% - a slight pale pink measles-like rash between the 7th and 12th days.

Reactions to the mumps vaccine are also rare, sometimes in the period from the 4th to the 12th day there is an increase in temperature and catarrh for 1-2 days. Very rarely there is an increase in the parotid salivary glands (within a period of up to 42 days).

Reactions to the rubella vaccine in children are not severe and are rare - short-term subfebrile temperature, hyperemia at the injection site, less often lymphadenitis. In 2% of adolescents, in 6% of people under 25 and in 25% of women over 25, from the 5th to the 12th day after vaccination, there is an increase in the occipital, cervical and parotid lymph nodes, short-term rashes, joint pain and arthritis (usually knee and wrist joints ), which disappear within 2-4 weeks. After vaccination in the postpartum period, as well as 7 days after the onset of the menstrual cycle, complications are observed less often.

Data on rubella vaccination of pregnant women (more than 1,000 women who were unaware of its presence) showed that infection of the fetus occurs frequently (up to 10%), but no developmental disorders of the fetus have ever been detected.

Allergic reactions

In children with allergies, allergic rashes may occur both in the first days after vaccination and during the peak of the vaccine reaction; their frequency does not exceed 1:30,000, less common are urticaria, Quincke's edema, lymphadenopathy, hemorrhagic vasculitis. They are associated with an allergy to neomycin or other components of the vaccine. Foreign-made vaccines made on the culture of chicken embryo cells are practically devoid of ovalbumin, so they carry a minimal risk of developing a reaction, and only in children who react to it according to the immediate type. Therefore, an allergy to chicken protein is not a contraindication to vaccination with trivaccines. Skin tests before vaccination are also not required. Reactions are even less common when using ZIV and ZPV, which are prepared on the culture of Japanese quail embryo fibroblasts, although cross-reactions are possible.

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Cramps

If the temperature rises above 39.5° (more than 4 days - 1:14,000), febrile seizures may develop in susceptible children, usually lasting 1-2 minutes (single or repeated). Their prognosis is favorable; paracetamol should be prescribed to children with the corresponding anamnesis from the 5th day after vaccination. The risk of developing seizures in children with a personal, and especially family, history of afebrile seizures is extremely low, so they are a contraindication.

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CNS lesions

Gait disturbance or nystagmus for several days after the trivalent vaccine occurs at a rate of 1:17,000. Persistent severe CNS lesions after measles vaccination are very rare (1:1,000,000); the incidence of encephalitis in vaccinated individuals is even lower than in the general population. Measles vaccination reduces the incidence of subacute sclerosing panencephalitis (SSPE), so eradication of measles will probably also eliminate SSPE.

When using mumps vaccines from the L-3 strain, as well as Jeryl Lynn and RIT 4385, serous meningitis is registered extremely rarely (1:150,000 -1:1,000,000). Although the Urabe and Leningrad-Zagreb strains more often cause meningitis, experts and the WHO consider it possible to continue their use; the Urabe strain has not been registered in Russia.

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Stomach ache

Abdominal pain (pancreatitis) is extremely rare after the mumps vaccine. Orchitis is rare (1:200,000) and occurs up to 42 days after vaccination with a favorable outcome.

Thrombocytopenia

Thrombocytopenia after the use of the trivalent vaccine on days 17-20 is rarely observed (1:22 300, according to one study), it is usually associated with the influence of the rubella component. However, isolated cases of thrombocytopenia with complete recovery have been described after the use of the measles monovalent vaccine.

Contraindications to vaccination against measles, rubella and mumps

Contraindications to vaccination against measles, rubella and mumps are as follows:

• immunodeficiency states (primary and as a consequence of immunosuppression), leukemia, lymphomas, other malignant diseases accompanied by a decrease in cellular immunity;
• severe forms of allergic reactions to aminoglycosides, egg white;
• for mumps vaccine - anaphylactic reaction to measles vaccine and vice versa (common culture substrate);
• pregnancy (due to the theoretical risk to the fetus).

Vaccinations are administered after the acute illness or exacerbation of a chronic illness. Women being vaccinated should be warned of the need to avoid pregnancy for 3 months (in the case of Rudivax - 2 months); pregnancy during this period, however, does not require termination. Breastfeeding is not a contraindication to vaccination.

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Vaccination of children against measles, rubella and mumps with chronic pathology

Immunodeficiencies

Live vaccines are contraindicated for children with primary forms. Children infected with HIV (with symptoms and asymptomatic course), but without pronounced immunosuppression (according to the CD4 lymphocyte index) are vaccinated at the age of over 12 months. After drug or radiation immunosuppression, live vaccines are administered no earlier than 3 months, after the use of corticosteroids in high doses (more than 2 mg/kg/day or 20 mg/day for 14 days or more) - no earlier than 1 month after the end of the course of treatment.

Tuberculosis

Although measles often provokes an exacerbation of tuberculosis infection, such an effect of vaccination has not been noted; the administration of measles and other vaccines does not require a preliminary tuberculin test.

Patients receiving blood products

Patients receiving blood products are vaccinated against measles, rubella and mumps no earlier than 3 months later. If blood products are administered less than 2 weeks after these vaccines, the vaccination should be repeated.

Post-exposure prophylaxis of measles, mumps and rubella

Contact persons over 12 months of age who have not had measles and have not been vaccinated are given the vaccine in the first 3 days after contact. Post-exposure vaccination is also possible for children aged 6-12 months. An alternative to this, as for persons with contraindications to vaccination, is the administration of 1 or 2 doses (1.5 or 3.0 ml) of normal human immunoglobulin depending on the time elapsed since contact (most effective when administered before the 6th day).

Post-exposure prophylaxis of mumps is less effective, however, the introduction of ZPV to persons who have had contact with mumps outbreaks, who have not been previously vaccinated and have not suffered from this infection is regulated no later than the 7th day from the moment of detection of the first patient in the outbreak. At the same time, obviously, some children will be vaccinated within 72 hours after infection, the most favorable For the prevention of the disease, the introduction of normal human immunoglobulin upon contact does not guarantee the prevention of the disease.

All those who are not immune to rubella, except pregnant women, are subject to vaccination against rubella in the center of rubella infection, since vaccination in the first three days from the onset of contact reduces the risk of developing clinically expressed forms of the disease. However, given the early contagiousness of patients (see above), this recommendation is unlikely to be effective.

In case of contact of a pregnant woman with a rubella patient, her susceptibility should be determined serologically. In case of presence of IgG antibodies, the woman is considered immune. In the absence of antibodies, the analysis is repeated after 4-5 weeks: if the result is positive, termination of pregnancy is suggested; if the second sample does not contain antibodies, the analysis is taken after 1 month - the interpretation is the same.

The use of human immunoglobulin for post-exposure prophylaxis of rubella in pregnancy is not recommended and is only administered when the woman does not wish to terminate the pregnancy. Limited observations suggest that administration of a 16% solution of human immunoglobulin at a dose of 0.55 ml/kg may prevent infection or modify the course of the disease. However, a certain proportion of pregnant women who receive the drug may remain unprotected, and their children may have congenital rubella syndrome.