Vaccination against pneumococcal infection

Pneumococci cause the most frequent bacterial infection of humans, according to WHO, it causes 1.2 million deaths per year, more than 40% of deaths of children 0-5 years - community-acquired pneumonia in Russia 1.5 million per year, pneumococci cause 76% of in adults and up to 90% in children under 5 years old, including those complicated by pleurisy and destruction. Vaccination from pneumococcal infection significantly reduced the incidence of pneumococcal infection.

Although statistics of pneumococcal infection is not maintained, with an incidence of pneumonia 10-12 per 1000 children aged 0-5 years and 85% S. Pneumoniae in the structure of their pathogens, we get an indicator of the order of 1100 per 100 000 children, i.e. 100 thousand pneumococcal pneumonia in children 0-5 years per year. The indicator of pneumococcal bacteremia (10% of the number of pneumonia) is about 100 per 100,000 or 9,000 cases per year. These figures are very close to the figures in Europe and the United States.

The pneumococcal meningitis differs by special gravity, the frequency of which, according to A.E. Platonov, is about 8 per 100 000 children under 5 years old.

Pneumococcus is caused by 30-35% of acute otitis media, which is tolerated by almost every child. They are distinguished by a special severity, propensity to perforate the tympanic membrane and the development of otogenic intracranial complications; they most often require tympanostomy and cause recurrence of otitis.

Vaccination from pneumococcal infection: vaccines

Pneumococcal vaccines are divided into polysaccharide and protein conjugated vaccines; the latter differ in immunogenicity, beginning with the first months of life, whereas the first in children under 2 years of age are not immunogens.

Polysaccharide pneumococcal vaccines. In Russia, Pnevmo23 (sanofi pasteur) is registered - a mixture of purified capsular polysaccharides of 23 serotypes of pneumococcus, which includes 90% of the strains isolated from the blood and most of the strains found in Russia. A similar vaccine Pneumovax® 23 (Merckx Sharp and Dome, USA) is being registered. The vaccine is administered once.

Pneumococcal vaccines registered in Russia

Vaccine	Composition
Pneumo23 - 23-valent polysaccharide vaccine - sanofi Pasteur, France	Polysaccharides (25 μg each) of serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, PA, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F , 33F; preservative phenol 1,25 mg. Inoculation once per os or in / m - 1 dose of 0.5 ml from the age of 2 years. Repeated vaccination - no earlier than 3 years. Store at 2-8 °, shelf life 2 years.
Pneumovax® 23 - 23 valence polysaccharide vaccine - Merck Sharp and Dome (filed for registration)
Prevenar - 7-valent conjugated vaccine - Wyeth, USA	The protein-conjugated polysaccharides of serotypes 4, 6B, 9V, 14,19F, 18C, 23F are administered together with DTP three times + revaccination

The Ministry of Healthcare and Social Development recommends Pneumo23 for persons> 65 years of age, as well as for:

• persons with chronic heart diseases (including heart failure, cardiomyopathy), lungs (including COPD, emphysema, bronchial asthma with frequent ARI), liver (including cirrhosis of the liver ) and kidneys (chronic renal failure, nephrotic syndrome) ;
• patients with diabetes mellitus;
• persons older than 2 years with functional or anatomic aspiration, cerebrovascular accident, cochlear implantation, deficiency of complement components;
• patients with oncohematological diseases, HIV infection, neutropenia, transplant recipients receiving immunosuppressive therapy;
• persons in collectives, especially before admission (kindergartens, army);
• often ill children, including those infected with tuberculosis.

Conjugated with protein pneumococcal vaccine Prevenar is used at the age of 2 months, its 7 serotypes cover 87% of pneumococcal isolates from sick children in the US and a number of other countries, similar vaccination efficiency can be expected in Russia (the serotypic pneumococcal landscape in Russia and the US is similar) . Pneumococcal vaccine is administered 3-fold together with DTP with booster at 18 months, there are data on the effectiveness of 2-fold vaccination (in the second half of the year) with revaccination, 2-fold vaccination in the 2nd year and a single vaccination in 2-5 years . Since the 7-valent vaccine does not include a number of important serotypes (1, 3, 5, 19A), a 13-valent Prevenar is planned.

Immunity

Pneumo23 in persons> 2 years of age forms protective levels of antibodies to the 3rd and 4th week, which persist up to 5-8 years. Revaccination (once 0.5 ml) is indicated in immunodeficiencies (including with asplenia and persons older than 65 years) not earlier than 3 years later. The growth of antibodies titer was 2-4 times higher in patients with diabetes, renal and rheumatoid diseases, especially when Pnevmo23 was administered with Grippol. In HIV + individuals, the vaccine is immunogenic, but the concentration of antibodies decreases more rapidly, so that it is shown to be re-vaccinated after 5 years (in children under 10 years - after 3 years). The same applies to children with nephrotic syndrome, who usually require a second vaccination after 20-22 months. Postponed pneumococcal infection (regardless of the reliability of the diagnosis) is not a contraindication to vaccination.

Conjugated vaccines induce a type-specific T-cell immune response and immunological memory: with the subsequent administration of a polysaccharide vaccine, the vaccinees show an increase in antibody titers (boosting). Pneumococcal vaccine also creates immunity to mucous membranes, which reduces the carriage among children who usually have a high density of the microbial population. With this, most probably, the effect of collective immunity is associated.

Epidemiological effectiveness of polysaccharide vaccines from pneumococcal infection

Efficacy Pneumo23 for the prevention of pneumonia, reaching 80%, was shown in the vaccination of adults aged 18-21 in organized groups, incl. Military: during 2-5 months after inoculation, the incidence of ARI decreased by 2.2 times, bronchitis - by 13 times, pneumonia - by 6.1 times. The effectiveness of the vaccine against bacteremic forms of pneumococcal infection (complicated pneumonia, meningitis, etc.) ranges from 56% to 81%.

The effectiveness of the vaccine at the age of 55 years was 93%, at the age of 55-64 years - 88%, at the age of 65-74 - 80%, at the age of 75 years - 67%. Vaccination of people older than 65 years was reduced by 45% risk of pneumonia, 41% - the risk of invasive infection, 26% - the risk of hospitalization and 41% - death.

Immunogenicity Pneumo23 in patients with broncho-pulmonary and cardiovascular diseases is similar to that of healthy patients (protective efficacy is about 69%). This figure in people with asplenia is 77%.

Vaccination of children with Pnevo vaccine23 in the children's homes has led to a reduction in the incidence of pneumococcal transport from 40 to 15%, and among frequently ill children - from 64 to 12%, which prevents the spread of resistant strains among risk groups. Along with this, often ill children had several times decreased overall respiratory incidence. The frequency of ARI in children with chronic lung diseases decreased by 1.7 times, and the frequency of exacerbations - 1.6 times. A positive effect - a decrease in the severity of bronchial asthma and a decrease in the incidence of ARI is noted in 60% of children. The combination of Pneumo23 with the Act-Hib vaccine reduces the incidence of SARS and otitis relapse 3 times.

Efficacy Pneumo23, thus, manifests itself as a specific action - a decrease in pneumococcal morbidity and carriage, and nonspecific, probably associated with the stimulation of the T helper-1 system. Its more pronounced effect compared with the bacterial lysates taken inside or in the aerosol (also including pneumococcal polysaccharides) appears to be due to the fact that it is administered parenterally.

Pneumococcal vaccine Pneumo23 effectively combines with influenza vaccines: thus, its administration, together with the vaccine Vaxigrip, to children infected with mycobacteria of tuberculosis, reduced the incidence of ARI, including bronchitis and pneumonia, by 92.8% (13.9 times); when Pneumo23 was used only, the incidence decreased by more than 7 times. Co-administration of Pnevmo23 and Vaxigrip vaccines to these contingents was recommended by the Research Institute of Phthisiopulmonology of the MMA named after M.Sc. Sechenov Ministry of Health and the RF.

Efficacy of Pneumovax® 23 for invasive infections in people at risk with diabetes is 84%, CHD 73%, heart failure 69%, lung diseases including COPD and asthma 65%, and in people over 65 years 75%.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]

The effectiveness of conjugated vaccines from pneumococcal infection

Already the first results of using the Prevenar vaccine showed that it prevents 83% of meningitis caused by vaccine serotypes. For all radiologically confirmed pneumonia, the incidence rate decreased by 20.5%, with the incidence of hospitalizations falling from 11.5 to 5.5 cases per 1000 children (by 52.4%) for pneumonia of any etiology, and the frequency of outpatient visits with 99.3 to 58.5 cases per 1000 children (by 41.1%).

According to the CDC, Prevenar mass vaccination reduced the incidence of bacteremic forms of pneumococcal infection in children 0-4 years of age caused by pneumococcal vaccines from 81.9 to 1.7 per 100 000. There was a certain increase in bacteremia caused by non-entering vaccine serotypes (from 16.8 to 21.7), but the total number of bacteremia decreased 4-fold - from 98.7 to 23.4 per 100,000.

Significantly changed and the incidence of pneumococcal meningitis. In the US, in children 0-2 years, it declined from 2000 to 2004. From 7.7 to 2.6, and mortality from 0.37 to 0.18 per 100,000, i.e. For 4 years, 1600 cases of meningitis of this etiology were prevented. In Spain, the incidence of pneumococcal meningitis (per 100,000 children 0-5 years) decreased due to vaccination by 54% - from 6.14 in 2001 to 2.86 in 2006.

Mass vaccination of young children has formed a collective immunity: in the United States, bacteremia pneumonia became less frequent in non-vaccinated children 5-15 years (38%), and in adults (47% at the age of 15-45, 20% in 45 -65 year olds), and by 36% - in persons older than 65 years. The incidence of pneumococcal meningitis decreased by 33%, and the death rate of persons older than 65 years - by 44%.

Pneumococcal vaccine protects from 80% of strains of pneumococcus with intermediate and 100% with high resistance to penicillin.

With a 57% decrease in the incidence of otitis caused by vaccine serotypes, the overall effect of vaccination was significantly lower (6-9%) due to the maintenance of morbidity caused by other pathogens and an increase in the incidence of otitis caused by other pneumococcal serotypes (by 33%). More pronounced decrease in recurrent otitis (by 16%) and severe forms requiring tympanostomy (by 25%). The carrying of vaccine serotypes was halved, but their place is taken by other serotypes, so the overall effect is not so significant.

Pneumococcal vaccine Prevenar also successfully combines with influenza, and this combination (in the autumn Infljuvak + Prevenar twice with an interval of 4-8 weeks) in children 18-72 months resulted in a reduction in the frequency of febrile respiratory episodes in comparison with the control group receiving HBV epidemic season by 25%, whereas only Inffluvak - by 13%. At the same time, the decrease in confirmed cases of influenza in the Influvak + Prevenar group and only Influvak was similar (51 and 52%), the level of decrease in the frequency of otitis media was not significantly different (57 and 71%). Outside the influenza season The differences between the experimental groups and the control group were unreliable.

Although the cost of the conjugate vaccine is significant, mass vaccination in the US gives a noticeable economic effect. The overall estimated direct costs of the health system associated with hospitalizations and outpatient visits for pneumonia of any etiology for young children decreased from an average annual rate of $ 688.2 million between 1997 and 1999 to $ 376.7 million in 2004 (a decrease of 45.3%, that is, approximately $ 310 million). Given the decline in the incidence of all ages under the influence of children's vaccination, the economic effect is estimated to be significant.

WHO estimates that if vaccinated with 7-valent conjugated vaccine for all children in 72 developing countries, it is possible to prevent 407 000 deaths annually. Given the high effectiveness of this vaccine, WHO considers it to be a priority to include it in the National Calendars of Immunoprophylaxis.

Contraindications for vaccination against pneumococcal infection

There are no special contraindications for both vaccines, except for reactions to the previous dose of the vaccine. Pneumococcal vaccine Pnevmo23 is administered at least 10 days before the start of immunosuppressive therapy because of the possibility of a decrease in the level of antibodies at a later onset. Vaccination of pregnant women is possible only in the 3rd trimester and without extreme necessity is not recommended.

[16], [17], [18], [19], [20], [21], [22], [23], [24], [25]

Vaccination reactions after vaccination against pneumococcal infection

Pneumo23 administration in 5% of vaccinated patients is possible local reaction, usually weak (redness, soreness) up to 48 hours. Vaccination against pneumococcal infection can be carried out year-round and combined in one day with any other vaccines (except BCG). Complications are rare: rash, joint pain. In patients with remission of thrombocytopenic purpura, relapses are rarely reported after 2-14 days after vaccination for up to 2 weeks. Very rare anaphylactic reactions are described.

Pneumococcal vaccine Prevenar is well tolerated by children, the experience of more than 20 million vaccinations has not revealed serious complications. However, the vaccine often gives local reactions in the form of redness and swelling, fever up to 38 °, irritability, sleep disorders; about 5% of children give a temperature of more than 39 °.