Vaccination against pneumococcal infection

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

Although statistics on pneumococcal infection are not kept, with a pneumonia incidence rate of 10-12 per 1000 children aged 0-5 years and 85% S. pneumoniae in the structure of their pathogens, we get a rate of about 1100 per 100,000 children, i.e. 100 thousand pneumococcal pneumonias in children aged 0-5 years per year. The rate of pneumococcal bacteremia (10% of the number of pneumonias) is about 100 per 100,000 or 9,000 cases per year. These rates are very close to the figures in Europe and the USA.

Pneumococcal meningitis is particularly severe, the frequency of which, according to A.E. Platonov, is approximately 8 per 100,000 children under 5 years of age.

Pneumococcus is responsible for 30-35% of acute otitis media, which almost every child suffers from. They are particularly severe, prone to perforation of the eardrum and development of otogenic intracranial complications; they most often require tympanostomy and cause relapses of otitis.

Pneumococcal Vaccination: Vaccines

Pneumococcal vaccines are divided into polysaccharide and protein-conjugated vaccines; the latter are immunogenic starting from the first months of life, while the former are not immunogenic in children under 2 years of age.

Polysaccharide pneumococcal vaccines. Pneumo23 (Sanofi Pasteur) is registered in Russia - a mixture of purified capsular polysaccharides of 23 pneumococcal serotypes, which include 90% of strains isolated from blood and most strains found in Russia. A similar vaccine Pneumovax® 23 (Merckx Sharp and Dohme, USA) is being registered. The vaccine is administered once.

Pneumococcal vaccines registered in Russia

Vaccine	Compound
Pneumo23 - 23-valent polysaccharide vaccine - Sanofi Pasteur, France	Polysaccharides (25 mcg 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. Single vaccination subcutaneously or intramuscularly - 1 dose of 0.5 ml from the age of 2 years. Revaccination - not earlier than after 3 years. Store at 2-8°, shelf life is 2 years.
Pneumovax® 23 - 23-valent polysaccharide vaccine - Merck Sharp & Dohme (submitted for registration)
Prevenar - 7-valent conjugate vaccine - Wyeth, USA	Protein-conjugated polysaccharides of serotypes 4, 6B, 9V, 14,19F, 18C, 23F, administered together with DPT three times + revaccination

The Ministry of Health and Social Development recommends Pneumo23 for people over 65 years old, as well as for:

• persons with chronic diseases of the heart (including heart failure, cardiomyopathy), lungs (including COPD, emphysema, bronchial asthma with frequent acute respiratory infections), liver (including liver cirrhosis ) and kidneys (chronic renal failure, nephrotic syndrome);
• patients with diabetes;
• persons over 2 years of age with functional or anatomical asplenia, cerebrospinal fluid rhinorrhea, cochlear implantation, complement component deficiency;
• patients with oncohematological diseases, HIV infection, neutropenia, transplant recipients receiving immunosuppressive therapy;
• individuals in groups, especially before entering (kindergartens, army);
• frequently ill children, including those infected with tuberculosis.

The protein-conjugated pneumococcal vaccine Prevenar is used from the age of 2 months, the 7 serotypes included in it cover 87% of pneumococcal isolates from sick children in the USA and a number of other countries, similar vaccination efficiency can be expected in Russia (the serotype landscape of pneumococci in Russia and the USA is similar). The pneumococcal vaccine is administered 3 times together with DTP with revaccination at 18 months, there are data on the efficiency of 2-fold vaccination (in the 2nd half of the year) with revaccination, 2-fold vaccination in the 2nd year and a single vaccination at 2-5 years. Since the 7-valent vaccine does not include a number of important serotypes (1, 3, 5, 19A), it is planned to create a 13-valent Prevenar.

Immunity

In individuals >2 years of age, Pneumo23 forms protective antibody levels by the 3rd-4th week, which persist for up to 5-8 years. Revaccination (a single dose of 0.5 ml) is indicated for immunodeficiencies (including asplenia and individuals over 65 years of age) not earlier than after 3 years. A 2-4-fold increase in antibody titers was obtained in patients with diabetes, renal and rheumatoid diseases, especially when Pneumo23 was administered together with Grippol. In HIV+ individuals, the vaccine is immunogenic, but the antibody concentration decreases faster, so they are recommended to be re-vaccinated after 5 years (in children under 10 years of age - after 3 years). The same applies to children with nephrotic syndrome, who usually require re-vaccination after 20-22 months. A history of pneumococcal infection (regardless of the reliability of the diagnosis) is not a contraindication to vaccination.

Conjugate vaccines induce a type-specific T-cell immune response and immunological memory: subsequent administration of a polysaccharide vaccine results in an increase in antibody titers (boosting) in vaccinated individuals. The pneumococcal vaccine also creates mucosal immunity, reducing carriage among children, who usually have a high density of the microbial population. This is most likely the cause of the herd immunity effect.

Epidemiological effectiveness of polysaccharide vaccines against pneumococcal infection

The effectiveness of Pneumo23 for pneumonia prevention, reaching 80%, was demonstrated in the vaccination of adults aged 18-21 in organized groups, including military ones: within 2-5 months after vaccination, the incidence of acute respiratory infections 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 vaccine efficacy was 93% in those under 55, 88% in those aged 55-64, 80% in those aged 65-74, and 67% in those over 75. Vaccination of those over 65 reduced the risk of pneumonia by 45%, the risk of invasive infection by 41%, the risk of hospitalization by 26%, and death by 41%.

The immunogenicity of Pneumo23 in patients with bronchopulmonary and cardiovascular diseases is similar to that in healthy individuals (protective efficacy is about 69%). This figure in individuals with asplenia is 77%.

Vaccination of children with the Pnevo23 vaccine in children's homes has reduced the frequency of pneumococcal carriage 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, the general respiratory morbidity has decreased several times in frequently ill children. The frequency of acute respiratory infections in children with chronic lung diseases has decreased by 1.7 times, and the frequency of exacerbations - by 1.6 times. A positive effect - a decrease in the severity of bronchial asthma and a decrease in the frequency of acute respiratory infections - was noted in 60% of children. The combination of Pneumo23 with the Act-Hib vaccine reduces the frequency of acute respiratory viral infections and otitis relapses by 3 times.

The effectiveness of Pneumo23 is thus manifested both by a specific action - a decrease in pneumococcal morbidity and carriage, and by a non-specific action, probably associated with stimulation of the T-helper-1 system. Its more pronounced effect compared to bacterial lysates taken orally or in an aerosol (also including pneumococcal polysaccharides) is apparently associated with the fact that it is administered parenterally.

The pneumococcal vaccine Pneumo23 is effectively combined with influenza vaccines: for example, its administration together with the vaccine Vaxigrip to children infected with tuberculosis mycobacteria reduced the incidence of acute respiratory infections, including bronchitis and pneumonia, by 92.8% (13.9 times); when using only Pneumo23, the incidence rate decreased by more than 7 times. The combined administration of Pneumo23 and Vaxigrip vaccines to these contingents is recommended by the Sechenov Moscow Medical Academy Research Institute of Phthisiopulmonology of the Ministry of Health and Social Development of the Russian Federation.

The effectiveness of Pneumovax® 23 against invasive infections in people at risk with diabetes is 84%, coronary heart disease - 73%, heart failure - 69%, lung diseases, including COPD and asthma - 65%, and in people over 65 years of age - 75%.

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Efficacy of conjugate vaccines against pneumococcal infection

The first results of the Prevenar vaccine application showed that it prevents 83% of meningitis cases caused by vaccine serotypes. For all radiologically confirmed pneumonia cases, the incidence rate decreased by 20.5%, with the hospitalization rate for pneumonia of any etiology decreasing from 11.5 to 5.5 cases per 1,000 children (by 52.4%) and the outpatient visit rate decreasing from 99.3 to 58.5 cases per 1,000 children (by 41.1%).

According to the CDC, mass vaccination with Prevenar reduced the incidence of bacteremic pneumococcal disease in children aged 0-4 years caused by pneumococci included in the vaccine from 81.9 to 1.7 per 100,000. At the same time, there was a slight increase in bacteremia caused by serotypes not included in the vaccine (from 16.8 to 21.7), but the overall incidence of bacteremia decreased fourfold - from 98.7 to 23.4 per 100,000.

The incidence of pneumococcal meningitis has also changed significantly. In the USA, it decreased from 7.7 to 2.6 in children aged 0-2 years between 2000 and 2004, and mortality from 0.37 to 0.18 per 100,000, i.e. 1,600 cases of meningitis of this etiology were prevented in 4 years. In Spain, the incidence of pneumococcal meningitis (per 100,000 children aged 0-5 years) decreased by 54% due to vaccination - from 6.14 in 2001 to 2.86 in 2006.

Mass vaccination of young children has created herd immunity: in the USA, bacteremic pneumonia has become less common among unvaccinated children aged 5-15 (by 38%), and among adults (by 47% at the age of 15-45, by 20% at the age of 45-65), and by 36% among people over 65. The incidence of pneumococcal meningitis has also decreased by 33%, and the mortality rate among people over 65 has decreased by 44%.

The pneumococcal vaccine protects against 80% of pneumococcal strains with intermediate resistance and 100% with high resistance to penicillin.

With a 57% reduction in the incidence of otitis caused by vaccine serotypes, the overall impact of vaccination was significantly lower (6-9%) due to the persistence of morbidity caused by other pathogens and an increase in the frequency of otitis caused by other pneumococcal serotypes (by 33%). A more pronounced reduction was observed in recurrent otitis (by 16%) and severe forms requiring tympanostomy (by 25%). The carriage of vaccine serotypes was halved, but their place was taken by other serotypes, so the overall effect was not as significant.

The pneumococcal vaccine Prevenar also combines successfully with the influenza vaccine, and such a combination (in the fall, Influvac + Prevenar twice with an interval of 4-8 weeks) in children aged 18-72 months led (in comparison with the control group that received HBV) to a decrease in the frequency of febrile respiratory episodes during the epidemic season by 25%, while only Influvac - by 13%. At the same time, the decrease in confirmed cases of influenza in the Influvac + Prevenar group and only Influvac was similar (51 and 52%), the level of decrease in the frequency of otitis media did not differ significantly (57 and 71%). Outside the influenza season, the differences between the experimental groups and the control were insignificant.

Although the cost of the conjugate vaccine is significant, mass vaccination in the United States has produced significant economic benefits. Total estimated direct health care costs associated with hospitalizations and outpatient visits for pneumonia of any cause in young children decreased from an average annual value of $688.2 million during 1997–1999 to $376.7 million in 2004 (a decrease of 45.3%, or approximately $310 million). Given the reduction in incidence at all ages due to childhood vaccination, the economic benefits are estimated to be significant.

According to WHO calculations, if all children in 72 developing countries are vaccinated with the 7-valent conjugate vaccine, 407,000 deaths could be prevented annually. Given the high efficacy of this vaccine, WHO considers its inclusion in National Immunoprophylaxis Calendars a priority.

Contraindications to vaccination against pneumococcal infection

There are no specific contraindications for either vaccine, except for reactions to the previous dose of the vaccine. The pneumococcal vaccine Pneumo23 is administered at least 10 days before the start of immunosuppressive therapy due to the possibility of a decrease in antibody levels with a later start. Vaccination of pregnant women is possible only in the 3rd trimester and is not recommended unless absolutely necessary.

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Vaccination reactions after vaccination against pneumococcal infection

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

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