Pneumococcal disease in people under 19 years of age
Acute otitis media is one of the most common diagnoses associated with pediatric outpatient medical visits (8Prescribing antibiotics9). According to a recent analysis using administrative data, 20,800 episodes of acute all-cause otitis media per 100,000 person-years occurred among U.S. persons under 18 years of age during 2018, with a higher incidence in younger age groups (10). During 2015–19, in a group of 319 US children aged 6–36 months with clinically diagnosed acute otitis media, Streptococcus pneumoniae It was detected in the middle ear fluid in 24% (11); 9% of these children developed a PCV13 serotype (including 6°C), and 8% developed one of the serotypes included in PCV15 but not in PCV13 (serotypes 22F and 33F) (11). Additional analysis using administrative data estimated that among people under 18 years of age, 1,280 to 3,990 episodes of healthcare use occurred per 100,000 person-years in 2014 for all causes of pneumonia (12), and that during the period 2018-2019, there were 87 to 680 hospitalizations per 100,000 population due to all-cause pneumonia (13). Using population monitoring data, Pulmonary pulmonary It was detected in 4% of people under 18 years of age who were hospitalized with community-acquired pneumonia; The attributable proportion of pneumococcal and serotype distribution among all causes of pneumonia in children and adolescents, however, has not been determined (14). According to the US multi-country surveillance, the incidence of IPD†† During 2018-2019 it was 7.2 per 100,000 children under 5 years old and 1.5 per 100,000 people aged 5-18 years. PCV13 serotypes accounted for 21% and 34% of HCV cases in children less than 5 years of age and subjects aged 5 to 18 years, respectively. Similarly, additional serotypes unique to PCV15§§ 15% and 23% caused IPD in children aged less than 5 years and people aged 5-18 years, respectively (15th).
PCV15 . immunity
Phase II and III randomized controlled trials (RCTs) evaluated immunity of PCV15 compared to PCV13 in healthy infants and children (16–19), people aged 5-17 years with sickle cell disease (20), and people aged 6 to 17 years with HIV infection (21). The following outcomes were measured 30 days after administration of 1 dose of PCV, as determined in the relevant study protocols: geometric mean (GMC) immunoglobulin G (IgG) concentration (GMC) (16–21), the proportion of participants meeting a serotype-specific IgG value of 0.35 micrometerg/ml (response rate) (16–19), and geometric mean phagocytosis activity in a subset of the study population (17And the20And the21). One phase III randomized controlled trial enrolled healthy children aged 42–90 days who received PCV13 or PCV15 at ages 2, 4, 6, and 12–15 months. Except for serum 6A GMC after dose 3, PCV15 met the criteria for non-inferiority¶¶ PCV13 of the 13 combined serotypes with respect to response rate after dose 3 and GMC ratio after dose 3 and after dose 4. PCV15 produced a statistically significantly higher immune response for serotype 3 compared to PCV13 (17). PCV15 met the criteria for non-inferiority compared to PCV13 for the two unique serotypes 22F and 33F (17).
A phase III randomized controlled trial enrolled healthy children aged 42–90 days who were randomized to five different arms who received 0–4 doses of PCV15 in combination with PCV13 to complete a 4-dose PCV series, to evaluate the interchangeable use of PCV13 and PCV15 (19). The IgG GMCs of the 13 combined serotypes measured after dose 4 in children who received 1 dose of PCV15 were generally comparable to children who completed their PCV series with only PCV13. Among naive or partially vaccinated subjects aged 7 months to 17 years who received compensatory doses of PCV, PCV15 elicited IgG GMCs compared to PCV13 for the 13 combined serotypes (18). Among children with sickle cell disease, a dose of PCV15 increased IgG GMC for six of the 13 common serotypes and for the two unique serotypes (20). Among the HIV-infected children, a dose of PCV15 increased IgG GMC for eight of the 13 common serotypes and for the two unique serotypes, compared to a dose of PCV13; A single dose of PCV15 followed by PPSV23 after 8 weeks resulted in increased IgG GMC for three of the 13 common serotypes compared to a dose of PCV13 followed by PPSV23, although IgG GMC for 22F and 33F were lower in those who received PCV15 followed by PPSV23 compared to those contained in those patterns. who received PCV13 followed by PPSV23 (21).
PCV15 سلامة Safety
The safety of PCV15 was evaluated in seven randomized controlled trials with 4,778 subjects aged 6 weeks to 17 years who received 1 dose of PCV15 (16–23). Two of these randomized controlled trials enrolling children and adolescents with sickle cell disease or HIV infection were evaluated separately. Of the remaining five studies that enrolled healthy children, four studies were also included in the assessment of immunogenicity (16–19). Three studies included preterm infants born at less than 37 weeks’ gestation (17And the19And the23). Across these five studies, four of the 4,540 children who received PCV15 developed serious adverse events*** that were considered vaccine-related, compared to one of the 2,655 children who received PCV13. Each of the randomized controlled trials that enrolled children with sickle cell disease or HIV infection was included in the immune assessment (20And the21). No serious adverse events considered to be related to the vaccine were reported in either study.
Given the similarities between the target population and the vaccine schedule used, a detailed safety assessment was performed combining data from three studies of healthy children who received 4 doses of PCV15 (3002) or PCV13 (1467) at ages 2, 4, 6, and 12-15 month (17And the19And the22And the23). The most common adverse events reported after any dose of PCV included irritability (75.1% in the PCV15 group vs 72.7% in the PCV13 group), somnolence (56.7% vs 59.3%), injection site pain (45.1% vs 43.5%), and Decreased appetite (39.1% vs. 36.0%). Febrile convulsions were reported in eight of 3,002 (0.3%) children who received PCV15, and three of 1,467 (0.2%) who received PCV. Almost all febrile convulsions (8 of 11, 73%) occurred 50 days after receiving PCV, and none were considered vaccine-related by the study investigators. Adverse events considered related to the vaccine were reported in 89.1% of children who received PCV15 and 86.4% of children in the PCV13 group. Two children (0.1%) who received PCV15 and none who received PCV13 had serious adverse events that were considered vaccine-related; Each of these children was hospitalized with fever after vaccination (after dose 1 and after dose 3). Maximum rectal temperature (or rectal equivalent) of 104°F (40°C) during the first seven days after vaccination 19 of 2,772 (0.7%) children who received a fourth dose of PCV15 and three of 1287 (0.2) were reported ) %) who received PCV13.
Two economic models (the CDC model and Merck model) have evaluated the cost-effectiveness comparing the use of PCV15 and PCV13 according to the 4-dosing series currently recommended for children under 2 years of age (24). It was hypothesized that PCV15 and PCV13 have the same vaccine efficacy against disease caused by the thirteen serotypes present in PCV13. For PCV15, it was assumed that the efficacy against the two additional serotypes was comparable to the overall efficacy against disease caused by the serotypes present in PCV. In the CDC model, the efficacy of PCV15 against IPD caused by two additional serotypes was assumed to be 86% and the efficacy against IPD caused by most other serotypes (except serotype 3 and 19F) was assumed to be 86%. The efficacy against serotypes 3 and 19F has been assumed to be lower than that against other PCV serotypes (25). In the Merck model, the efficacy of PCV15 against IPD caused by the two additional serotypes was assumed to be 86%, and the efficacy against other serotypes was assumed to range from 80% to 100%. In both models, the use of PCV15 instead of PCV13 for routine childhood immunization was cost-saving††† Across all scenarios examined, including those in which PCV15 costs per dose§§§ It ranged from $4 less to $2 more than the cost of PCV13 per dose.
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