Analysis of Invasiveness of Pneumococcal Serotypes and Clones Circulating in Portugal before Widespread Use of Conjugate Vaccines Reveals Heterogeneous Behavior of Clones Expressing the Same Serotype

Abstract

To estimate the invasive disease potential of serotypes and clones circulating in Portugal before extensive use of the seven-valent pneumococcal conjugate vaccine, we analyzed 475 invasive isolates recovered from children and adults and 769 carriage isolates recovered from children between 2001 and 2003. Isolates were serotyped and genotyped by pulsed-field gel electrophoresis, and a selection of isolates were also characterized by multilocus sequence typing. We found that the diversities of serotypes and genotypes of pneumococci responsible for invasive infections and carriage were identical and that most carried clones could also be detected as causes of invasive disease. Their ability to do so, however, varied substantially. Serotypes 1, 3, 4, 5, 7F, 8, 9N, 9L, 12B, 14, 18C, and 20 were found to have an enhanced propensity to cause invasive disease, while serotypes 6A, 6B, 11A, 15B/C, 16F, 19F, 23F, 34, 35F, and 37 were associated with carriage. In addition, significant differences in invasive disease potential between clones sharing the same serotype were found among several serotypes, namely, 3, 6A, 6B, 11A, 14, 19A, 19F, 22F, 23F, 34, and NT. This heterogeneous behavior of the clones was found irrespective of the serotype's overall invasive disease potential. Our results highlight the importance of the genetic background when analyzing the invasive disease potential of certain serotypes and provide an important baseline for its monitoring following conjugate vaccine use. Continuous surveillance should be maintained, and current research should focus on uncovering the genetic determinants that contribute to the heterogeneity of invasive disease potential of clones sharing the same serotype.

Clonal Evolution Leading to Maintenance of Antibiotic Resistance Rates among Colonizing Pneumococci in the PCV7 Era in Portugal

“…Clearly, other factors beyond the capsule and the resistance determinants which may be concealed in the wider genome background of such clones may play a role. Such factors may be related to increased fitness and transmission and enhanced capacity to evade the host immune system or escape vaccine pressure (31).…”

Clonal Distribution of Common Pneumococcal Serotypes Not Included in the 7-Valent Conjugate Vaccine (PCV7): Marked Differences between Two Ethnic Populations in Southern Israel

“…While it is widely accepted that the capsular type is the key determinant of the ability of pneumococci to cause disease (3,4,12,(29)(30)(31), the extent of the additional role of other determinants has not yet been fully clarified. A single pneumococcal serotype typically includes a number of genetically divergent clones (based on a comparison of sequence types deposited at http://www.mlst .net), presumably as a consequence of the occasional horizontal transfer of the capsular biosynthetic genes into new lineages (3).…”

Estimation of the invasive disease potential of Streptococcus pneumoniae in children by the use of direct capsular typing in clinical specimens

“…In the present study, we aimed to add the molecular techniques for both the detection and the serotyping of the pneumococcus. It has already been proven that molecular techniques greatly improve the detection of pneumococcus, but, to date, most of the invasiveness studies published have utilized serotyping techniques based on culture [5,16,[18][19][20]. Even these studies that adopt molecular techniques for the identification of the pneumococcal capsule usually require previous isolation of the strain [21].…”

“…Also, the significance in the changes in serotypes during the study period and in the association between serotypes and multiple colonization was tested by the two-tailed Fisher's exact test, using the same cutoff p-value. The resulting p-values were corrected for multiple testing by controlling the false discovery rate (FDR) to ≤0.05 through the Benjamini and Hochberg method, as previously described [15,16]. Simpson's index of diversity (SID) was used to measure the collections' diversity via the website http://www.comparingpartitions.info [17].…”