Introduction: Streptococcus pneumoniae is a leading cause of morbidity and mortality worldwide. Widespread infant vaccination with pneumococcal conjugate vaccines (PCVs) substantially reduced ...vaccine-serotype pneumococcal disease by direct protection of immunized children and indirect protection of the community via decreased nasopharyngeal carriage and transmission. Essential to grasping the public health implications of pediatric PCV immunization is an understanding of how PCV formulations impact carriage.
Areas covered: Using clinical evidence, this review examines how the immune response to PCVs is associated with subsequent nasopharyngeal carriage reduction in vaccinated infants and toddlers. By combining direct and indirect protection, carriage reduction results in a reduced spread of vaccine serotypes, and eventually, a decrease in vaccine serotype disease incidence in community members of all ages.
Expert opinion: The current review presents some of the aspects that influence the overall impact of PCVs on vaccine-serotype carriage, and thus, spread. The link between reduction of vaccine-serotype carriage and the eventual reduction of vaccine-serotype disease in the wider community is described by comparing data from current PCVs, specifically with respect to their ability to reduce carriage of some cross-reacting serotypes (i.e. 6A versus 6B and 19A versus 19F).
Summary Otitis media is a common childhood infection of the middle ear and a major cause of morbidity. This multifactorial disease manifests as a spectrum of clinical syndromes from uncomplicated ...acute otitis media to more complex recurrent and chronic cases (frequently polymicrobial), with the major pathogens involved being Streptococcus pneumoniae and non-typeable Haemophilus influenzae . Pneumococcal conjugate vaccines (PCVs) target only a few serotypes that cause otitis media; however, results from studies suggest that existing PCVs can prevent early episodes of disease associated with vaccine serotypes, resulting in a reduction of subsequent complex cases caused by non-vaccine serotypes and other otopathogens, which contribute considerably to the disease burden. In this Review, we discuss the role of pneumococcus in the disease continuum and assess clinical evidence showing the effect of prevention of early episodes on the complex interplay between bacterial species implicated in otitis media.
In an Israeli Ministry of Health database, 136 definite or probable cases of myocarditis were detected among 5 million vaccinated persons. The rate ratio after two doses as compared with unvaccinated ...persons was 2.35, with the highest risk among male recipients between the ages of 16 and 19 years.
Summary Reduction of drug-resistant Streptococcus pneumoniae (DRSP) by pneumococcal conjugate vaccines (PCVs) has recently become a reality. We now know that (1) most clinically significant DRSP ...strains belong to seven serotypes (6A, 6B, 9V, 14, 19A, 19F, 23F), (2) five (6B, 9V, 14, 19F, 23F) of the seven are constituents of heptavalent PCV (PCV7), and (3) the remaining two serotypes (6A, 19A) are immunologically related to serotypes in PCV7, but only 6A has been reduced by PCV7. Furthermore, PCVs can also reduce DRSP in unvaccinated individuals (herd immunity). PCVs lead to a reduction in antibiotic use, which is also potentially helpful to contain DRSP. Although a reduction in disease caused by most penicillin-resistant strains has been reported, reductions in intermediately penicillin-resistant strains has not been shown to the same degree, because of increased intermediate resistance among non-PCV7 serotypes. Serotype 19A, which is both antibiotic resistant and a common cause of disease, is not affected by PCV7, and is now increasing worldwide, including in countries without PCV7. Continued exposure of non-PCV7 serotypes to antibiotic pressure may reduce the overall impact of PCVs on DRSP. Further strategies include expansion of PCV serotype coverage, development of protein-based vaccines, and further limitation of antibiotic use.
Abstract Bacterial polysaccharide–protein conjugate vaccines ( Haemophilus influenzae type b Hib, pneumococcal and meningococcal conjugates) have revolutionized pediatric vaccination strategies. The ...widely used carrier proteins are tetanus toxoid (TT), diphtheria toxoid (DT) and diphtheria toxoid variant CRM197 protein, DT conjugates being in general less immunogenic. Multivalent conjugates using TT were found to be at risk for reduced polysaccharide responses, whilst multivalent CRM197 conjugates are at lower risk for this, but may be at higher risk of inducing bystander interference, particularly affecting Hib and hepatitis B immune responses. Novel carriers avoiding these issues could enable the further development of pediatric schedules and combinations.
Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. In this clinical trial, a single dose of nirsevimab resulted in a significantly lower incidence of ...medically attended RSV-associated lower respiratory tract infection than that with placebo.
Background. Otitis media (OM) is common in early childhood. Streptococcus pneumoniae caused approximately 30%–60% of episodes before the pneumococcal conjugate vaccine (PCV) era. The 7-valent PCV ...(PCV7) was introduced to the Israeli National Immunization Plan in July 2009, and was gradually replaced by the 13-valent PCV (PCV13) starting in November 2010. We aimed at assessing the impact of PCV7/PCV13 sequential introduction on pneumococcal and overall OM necessitating middle ear fluid culture in children aged <2 years in southern Israel. Methods. This was a prospective, population-based, active surveillance. Our medical center is the only one in the region, enabling incidence calculation. All pneumococcal episodes submitted for culture between July 2004 and June 2013 were included. Three subperiods were defined: pre-PCV, PCV7, and PCV13. Results. Overall, 6122 OM episodes were recorded, and 1893 were pneumococcal. Compared with the pre-PCV period, OM caused by PCV7 plus serotype 6A and the 5 additional PCV13 serotypes (5VT : 1, 3, 5, 7F, 19A) decreased by 96% and 85%, respectively (incidence rate ratios IRRs, 0.04 95% confidence interval {CI}, .02–.08 and 0.15 95% CI, .07–.30, respectively) in a 2-step pattern: In the PCV7 period, only OM caused by PCV7 + 6A serotypes was decreased; in the PCV13 period, 5VT OM rates decreased, along with an additional PCV7 + 6A OM reduction. A nonsignificant increase in non-PCV13 serotype OM was observed (IRR, 1.07 95% CI, .72–1.58). In total, 77% and 60% reductions of all-pneumococcal and all-cause OM incidences, respectively, were observed. Conclusions. A substantial 2-step reduction of pneumococcal OM rates, with near-elimination of PCV13 disease, was observed shortly after PCV7/PCV13 introduction.
Streptococcus pneumoniae (pneumococcus) is a major cause of worldwide mortality and morbidity, and to a large extent is vaccine-preventable. Nasopharyngeal carriage of pneumococcus precedes disease ...and is the source of pneumococcal spread between people. The use of vaccine effect on carriage as part of the vaccine licensure and post-vaccine introduction evaluation could facilitate and expand the licensure of new, life-saving pneumococcal vaccines and enable a comprehensive estimate of population effects after vaccine introduction. The authors provide a review of the evidence supporting pneumococcal carriage at the individual level as an immediate and necessary precursor to pneumococcal disease. Based on such a causal link between carriage and disease, the authors emphasize the role of information on pneumococcal carriage in vaccine trials and in public health decision-making.
Background. Pneumococcal conjugated vaccines (PCVs) impact on complex otitis media (OM; including recurrent, nonresponsive, and chronic OM with effusion) was greater than that on simple, acute OM in ...previous studies. Since complex OM is often a polymicrobial disease, we speculated that reduction of complex OM by PCVs would be associated with reduction of non-pneumococcal OM. Methods. In a prospective, population-based, active surveillance, all OM episodes submitted for middle ear fluid culture in children <3 years from 2004 through 2015 were included. Three sub-periods were established: pre-PCV, PCV7, and PCV13. Incidence rate ratios (IRRs) comparing the 3 periods were calculated for pneumococcal, nontypable Haemophilus influenzae (NTHi), Moraxella catarrhalis, Streptococcus pyogenes, and culture-negative OM. Results. Overall, 7475 episodes were included. Of all-NTHi cases in the pre-PCV period, 34% were mixed with Streptococcus pneumoniae. IRRs (95% confidence interval) comparing the pre-PCV to the PCV13 period were 0.02 (0.01-0.04), 0.12 (0.08-0.20), and 0.18 (0.15-0.21) for PCV7+6A serotypes, 5 additional PCV13 serotypes, and all-pneumococcal OM, respectively; non-PCV13 serotype episodes were not significantly reduced. IRRs for single NTHi, mixed NTHi + S. pneumoniae, and all-NTHi OM were 0.30 (0.25-0.35), 0.18 (0.13-0.24), and 0.25 (0.22-0.29), respectively. Moraxella catarrhalis, S. pyogenes, and culture-negative episodes were also significantly reduced. Conclusions. Both pneumococcal and non-pneumococcal OM episodes, enriched with complex cases, declined substantially in children <3 years following sequential PCV7/PCV13 introduction. The reduction in non-pneumococcal episodes may be attributed to early OM episodes prevention, resulting in a lower rate of complex, often non-pneumococcal OM.
Background. The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed to replace the 7-valent pneumococcal conjugate vaccine (PCV7) based on serological noninferiority criteria. To date no ...randomized PCV13 pediatric trial has included clinical endpoints. Methods. This randomized double-blind trial compared the impact of PCV13 versus PCV7 on nasopharyngeal (NP) colonization and immunogenicity. Healthy infants were randomized (1:1) to receive PCV7 or PCV13 at ages 2, 4, 6, and 12 months; NP swabs were collected at 2, 4, 6, 7, 12, 13, 18, and 24 months, and blood was drawn at 7 and 13 months. Rates of NP acquisition and prevalence, and serotype-specific immunoglobulin G (IgG) concentrations were assessed. Results. The per protocol analysis population included 881 PCV13 and 873 PCV7 recipients. PCV13 significantly reduced NP acquisition of the additional PCV13 serotypes 1, 6A, 7F, and 19A; the cross-reacting serotype 6C; and the common PCV7 serotype 19F. For serotype 3, and the other PCV7 serotypes, there were no significant differences between the vaccine groups. There were too few serotype 5 events to draw inference. The impact on prevalence at predefined time points was similar to that observed with NP acquisition. PCV13 elicited significantly higher IgG responses for PCV13 additional serotypes and serotype 19F, and similar or lower responses for 6/7 PCV7 serotypes. Conclusions. PCV13 resulted in lower acquisition and prevalence of NP colonization than PCV7 did for 4 additional PCV13 serotypes, and serotypes 6C and 19F. It was comparable with PCV7 for all other common serotypes. These findings predict vaccine effectiveness through both direct and indirect protection. Clinical Trials Registration. NCT00508742.
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