Prevenar experience

Vaccine 29S (2011) C26–C34

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Prevenar experience Adriano Arguedas a,b,∗ , Carolina Soley a , Arturo Abdelnour a a b

Instituto de Atención Pediátrica, San José, Costa Rica Universidad de Ciencias Médicas, San José, Costa Rica

a r t i c l e

i n f o

Article history: Received 27 June 2011 Accepted 27 June 2011

Keywords: Pneumococcus Conjugate vaccines Streptococcus pneumoniae Vaccines

a b s t r a c t Streptococcus pneumoniae is one of the leading bacterial pathogens causing invasive disease and noninvasive infections at both extremes of life: in children younger than 5 years and in elderly persons of 65 years or more. Pneumococcal infections result in substantial morbidity and mortality among children under 5 years of age; it is estimated that 1,600,000 deaths occur per year in that age range alone, mostly in developing countries, thus representing a serious public health problem around the globe. Infections caused by S. pneumoniae are considered by the World Health Organization (WHO) as the number one vaccine-preventable cause of death in children younger than 5 years of age. In 2000, the first heptavalent conjugated pneumococcal vaccine (PCV7) was licensed in the United States, differing from the already available non-conjugated polysaccharide pneumococcal vaccine in its ability to induce a protective immune response in children under 2 years of age. Initial efficacy studies in the United States with PCV7 revealed a 97.4% efficacy against invasive pneumococcal disease (IPD) caused by vaccine serotypes (4, 9V, 14, 19F, 23F, 18C and 6B). PCV7 was introduced into the National Immunization Program (NIP) of various countries starting in year 2000 and, after 11 years of use, the data confirm that PCV7 introduction resulted in a major reduction of S. pneumoniae IPD, non-bacteremic pneumonia, otitis media medical visits, the need for tympanic tubes, the number of cases of otorrhea and of various antimicrobial resistant strains in children 38 ◦ C in 0.8–46.9%, sleepiness in 13–52%, irritability in 18.3–60% and anorexia in 24.3% 3–7 days after vaccination [41,47–49]. In two clinical studies, percentages of side effects after application of PCV7 alone in children older than 3 years of age were the following: pain in the site of injection 8.2–39.1%, pain restricting movement in 15.7%, erythema in 24.6–40%, erythema >2 cm in 17.4%, indurations in 25.4–35.5%, and indurations >2 cm in 9.6% [48,50].

2.3. Immunogenicity

4. Efficacy and effectiveness

T-cell dependent conjugated vaccines stimulate protective mucosal immunity, resulting in IgA levels that are detectable in children’s and infants’ saliva, as well as inducing systemic immunity with quantifiable levels of lgG in serum [30,31]. Antibody levels necessary to prevent carriage or to prevent the disease itself are unknown. Besides determining the total antibody levels, it is necessary to determine the level of functional antibodies, most often by detecting opsonophagocytic activity (OPA). OPA testing is far from being standardized [32], but limited data indicate that an opsonic titer >1:8 confers protection. This is based on data obtained from animal models. PCV efficacy studies in infants suggest that after PCV7 administration, specific polysaccharide IgG concentrations of 0.2–0.35 ␮g/ml, determined by ELISA, are protective against IPD [33]. A WHO expert panel reviewed data obtained from studies carried out in the US and South Africa and determined that the minimal concentration of antibodies for all analyzed serotypes, using a second generation ELISA technique, should be equal or higher than 0.35 ␮g/ml in order to provide adequate immunogenicity. If a second generation technique is used, including a 22F assay, the titers may be somewhat lower. According to one analysis the cut-off value using the 22F assay is 0.22 ␮g/ml [34]. Various randomized trials with PCV7 report that approximately 82–100% of participants obtained serum titers higher than the minimum limits for protection [35–40]. In children aged 2–15 months, PCV7 with other childhood vaccines provided adequate antibody

PCV7 is currently the only vaccine with post implementation effectiveness data. All efficacy and effectiveness data to date demonstrate that PCV7 confers protection against pneumonia, otitis media, meningitis and other invasive diseases produced by S. pneumoniae [5]. 4.1. Invasive pneumococcal disease The prospective double-blind Northern California Kaiser Permanente Vaccine Study (NCKP), held between 1995 and 1999, randomized approximately 37,800 healthy children to receive either PCV7 or a control vaccine at the following ages: 2, 4, 6, and 12–15 months. The objective of the trial was to determine the efficacy of PCV7 against IPD. According to the per-protocol analysis, the efficacy of PCV7 was 97.4% (95% CI: 82.7, 99.9), whereas on the intention to treat analysis (ITT) the efficacy was 93.9% (95% CI: 79.6, 98.5) against IPD caused by vaccine serotypes (VT). According to the ITT analysis, vaccine efficacy, against VT and non-vaccine serotypes (NVT), was of 89.1% (95% CI: 73.7, 95.8) [37]. Between 1999 and 2003 in the US, the effectiveness of PCV7 against IPD caused by VT in children below 5 years of age declined from 80 cases per 100,000 inhabitants, to 4.6 per 100,000 inhabitants, meaning an overall 94% decline in IPD (95% CI: 92, 96). The global IPD incidence in this group of age declined 75% (95% CI: 72, 78); from 96.7 cases in 1999 to 23.9 in 2003 [48]. More recently, CDC has published an evaluation of the effect of the continued use

A. Arguedas et al. / Vaccine 29S (2011) C26–C34

of PCV7 on the incidence of IPD in children