The results of this study suggest that the simplified PCV-7 schedule of only three doses administered at 3, 5 and 11–12 months of age can significantly reduce the incidence of AOM and CAP, as well as the consumption of antibiotics. These major advantages become apparent immediately after the administration of the third dose and are maintained until at least the end of the 30th
month of life. To the best of our knowledge, this is the first study which showed the impact of PCV-7 administered at 3, 5 and 11–12 months of age on respiratory tract infections. Previous studies have shown that the positive effects of the 4-dose PCV-7 schedule on respiratory tract infections can be seen in children aged more than 36 months [27
] and, as both schedules lead to similar antibody levels [21
], it is possible that the global prevention of pneumococcal respiratory diseases in children vaccinated with the simplified schedule is even greater than that demonstrated by our study.
In our study, a between-group difference in the incidence of RTIs and LRTIs was clearly evident only after the 25th
month of age. These findings may be explained by the fact that, as the bacterial/viral RTI ratio increases with age [5
], the effect of pneumococcal vaccine appears more evident in children older than 2 years. On the basis of these results, one should consider the opportunity to give the vaccination as a single- or two-dose schedule in children older than one year of age. Although the effectiveness of these schedules has not been evaluated in this study, the vaccination in the first months of life permits to avoid or significantly reduce pneumococcal nasopharyngeal colonization with major benefits on respiratory morbidity [34
Although the higher rates of CAP among older unvaccinated children have no specific explanation, the global incidence of CAP in our unvaccinated children of all age groups was similar to that found in previous studies [36
]. However, the positive effect of PCV-7 on CAP prevention was greater than that previously reported with this vaccine [19
] and similar to that observed with the 9-valent pneumococcal vaccine [38
]. This was probably due to the fact that we considered only radiologically confirmed cases, the majority of which were severe enough to require hospitalisation.
The incidence of AOM in both of our groups fell within the previously reported range [39
], but was significantly lower in the children receiving PVC-7 during the individual follow-up periods as well as during the follow-up as a whole. The reduction in AOM in our study population was greater than that found in clinical trials carried out in the United States [16
] and Finland [17
], which demonstrated that the efficacy of PCV-7 was 6–9% against all cases of AOM and 50–60% against cases due to the pneumococcal serotypes included in the vaccine. The global reduction in the incidence of AOM in our PCV-7 group was 17%, and the reductions in the individual 6-month periods were respectively 9%, 19%, 18% and 19%. These results are similar to those obtained with the 9-valent pneumococcal conjugate vaccine by Dagan et al
], who suggested that the greater-than-expected effect of the vaccine may have been due to it better coverage against antibiotic-resistant strains of S. pneumoniae
], the large majority of which belong to a limited number of serotypes included in PCV-7 [34
]. We do not know the incidence of antibiotic-resistant S. pneumoniae
strains among our study children but, as recent data collected in Italy have demonstrated a significant increase in the prevalence of highly-resistant strains [44
], the explanation offered by Dagan et al
] may also apply to our study.
The fact that the children in our PCV-7 group received significantly fewer antibiotic courses than those in the control group indicates that the vaccine may reduce not only the risk of adverse events due to antibiotic use, but also the costs of medical treatment. The economic saving is further underlined by the fact that the children in the PCV-7 group required fewer hospitalisations due to CAP.
Results of this study are in line with those calculated in children of the same areas regarding the predicted effects of PCV-7 immunization in relation to the circulation of the different S. pneumoniae
serotypes and their role in nasopharyngeal colonization as well as in the determination of non-invasive diseases [32
]. In addition, one of the major advantages of the 3-dose schedule is the fact that this simplified scheme could be associated with a reduction of 25% in health care costs in comparison with the traditional 4-dose schedule. Moreover, when high pneumococcal vaccination coverage levels are reached, further medical and economical benefits due to the effect of herd immunity could be observed.
Our findings may be criticised on the grounds that they come from a single-blind, observational study rather than a double-blind, randomised, placebo-controlled trial, but an analysis of the characteristics of the study children showed that there were no differences between the subjects receiving PCV-7 and the controls. In particular, there were no between-group differences in the variables that can influence the carrier state of respiratory pathogens and contribute to the development of respiratory diseases. Moreover, all of the information regarding the diseases was verified by means of telephone interviews with the children's pediatricians, and only the data reported by them were used in the analysis. Finally, the total number of diagnosed illnesses other than respiratory diseases or AOM in both of our study groups was similar, thus suggesting that there was no difference in the attention paid by the parents to the diseases developed by their children. On the basis of all of the above, we believe that there is only a marginal risk of sampling bias influencing our data analysis and that the two groups are therefore comparable.