We have observed changes in clinical respiratory tract infections associated with pneumococci after the introduction of PCV in a Swedish County. Bacterial cultures were referred from a well-defined catchment area served by a single microbiological laboratory, and a large number of bacterial samples were compiled during 5 years, allowing comprehensive epidemiological evaluation. Two time periods, that is, 2 years prior to and 3 years after introduction of PCV were investigated. Three major findings can be concluded; i) upper respiratory tract isolates of S. pneumoniae decreased by more than a third; ii) a shift in the distribution of pneumococci from serotypes included in PHiD-CV10 to non-PHiD-CV10 serotypes; and, finally, iii) that the frequency of culture-verified S. pneumoniae isolates in patients with symptoms of AOM decreased significantly.
The efficacy of PCV vaccines on pneumococcal syndromes such as IPD, pneumonia, AOM and sinusitis has previously been thoroughly investigated [2–7]. Our study is important since it assesses the impact of PCV on pneumococci in the upper respiratory tract of all patients with signs of respiratory infection. These patients were in our study mainly attending outpatient clinics (family physicians), where antibiotic treatment is often considered. A lower incidence of pneumococcal isolates may thus reduce the need for antibiotics.
In pre-marketing studies, evidences of any effect of PCV on AOM are scarce. Our observation of a decrease in complicated AOM due to S. pneumoniae is, however, in concordance with several post-licensure studies. Tamir et al. found a reduction in episodes of severe pneumococcal AOM , and others have reported a decrease in AOM-related visits to hospitals and outpatient clinics . The decreased carriage of PCV serotypes in the population causes a reduced transmission of pathogenic bacteria, which could explain the decrease in AOM. It cannot be excluded that other factors, such as natural variation in AOM disease contributed to the reduction as presented in our study. Pneumococcal infection is often promoted by influenza virus. However, according to statistics from the Swedish Public Health Agency the influenza seasons were of “medium intensity” in 2007/2008 and of “high intensity” in 2011-2013 , and thus the observed decrease of pneumococcal isolates should not be attributed to milder influenza seasons.
The serotype replacement observed in this study is in concordance with previous publications . In studies on carriage of pneumococci in the nasopharynx of children, the phenomenon of serotype replacement has been suggested to maintain overall carriage, even after introduction of PCV . The vacant niche left by eradicated vaccine serotypes are replaced by non-vaccine strains. On the other hand, we analysed carriers of pneumococci having symptoms of respiratory tract infection and not passive carriage of pneumococci. The observation that non-vaccine isolates became less prevalent after introduction of PCV (Fig. 1) might be explained by a lower virulence among non-PCV serotypes as previously suggested . Cross-protection of capsule polysaccharides included in the vaccine could also have contributed to the overall reduction of clinical isolates found. Previous results from studies on PCV7 and PHiD-CV10, which both contain the serotype 6B capsule, have suggested significant cross-reactivity against serotype 6A, and subsequent protection from disease caused by this particular serotype [14, 25], findings that are supported also in the present study. In contrast, pneumococci carrying the 6C capsule emerged, and it has recently been recognized as an expanding serotype in the PCV era.
Pre-marketing studies highlighted cross-protection against non-vaccine serotype 19A, which is closely related to vaccine serotype 19F. However, in some countries with high PCV7 coverage, an increased pneumococcal disease caused by serotype 19A has occurred, and questioned the existence of serotype 19F-19A cross-protection by the PCV7. On the other hand, PHiD-CV10 has been found to induce higher anti-19A IgG titers in OPA (opsonophagocytosis) compared to PCV7, suggesting a superior immune response . Surprisingly, we found that the absolute and relative incidence of S. pneumoniae serotype19A increased during the observation period, and together with serotype 3 comprised 18.8 % of all S. pneumoniae 4 years after PCV introduction. Both serotypes 3 and 19A are included in PCV13, which raised the question of possible benefits for this vaccine in the study population. However, immunization with serotype 3 has been shown to induce a hyporesponse and the vaccine effect against this specific serotype is questioned . Another fact is that PCVs were included in the child immunization programme in order to protect against IPD in children, whereas the focus of the present study was on upper respiratory tract isolates. In our catchment area, serotypes 11A and 15B, none of which are included in the available conjugated vaccines, were among the most common serotypes after PCV introduction, a finding consistent with previous studies which have also found them to be emerging pneumococcal serotypes [28, 29].
There are a few limitations associated with our investigation. Firstly, samples may be taken for reasons other than those recommended by regional guidelines or clinical praxis. Some physicians may also be more prone to take nasopharyngeal swabs than others. However, we believe that these confounders are unlikely to have changed between the two time periods compared. Secondly, all pneumococcal isolates were not available for typing. The percentage of lost isolates was, however, evenly distributed prior to and after the introduction of PCV, and the missing isolates were considered as missing at random.