Temporal changes in nasopharyngeal carriage of Streptococcus pneumoniaeserotype 1 genotypes in healthy Gambians before and after the 7-valent pneumococcal conjugate vaccine

Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive pneumococcal disease. However, this invasive serotype is hardly found in nasopharyngeal asymptomatic carriage and therefore large epidemiological studies are needed to assess the dynamics of serotype 1 infection. Within the context of a large cluster randomized trial conducted in rural Gambia to assess the impact of PCV-7 vaccination on nasopharyngeal carriage, we present an ancillary analysis describing the prevalence of nasopharyngeal carriage of pneumococcal serotype 1 and temporal changes of its more frequent genotypes. Nasopharyngeal swabs (NPS) were collected before PCV-7 vaccination (December 2003–May 2004) and up to 30 months after PCV-7 vaccination. The post-vaccination time was divided in three periods to ensure an equal distribution of the number of samples: (1) July 2006–March 2007, (2) April 2007–March 2008 and (3) April 2008–Feb 2009. S. pneumoniae serotype 1 were genotyped by MLST. Serotype 1 was recovered from 87 (0.71%) of 12,319 NPS samples collected. In the pre-vaccination period, prevalence of serotype 1 was 0.47% in both study arms. In the post-vaccination periods, prevalence in the fully vaccinated villages ranged between 0.08% in period 1 and 0.165% in period 2, while prevalence in partly vaccinated villages was between 0.17% in period 3 and 1.34% in period 2. Overall, four different genotypes were obtained, with ST3081 the most prevalent (60.71%), followed by ST618 (29.76%). ST3081 was found only in post-vaccination period 2 and 3, while ST618 had disappeared in post-vaccination period 3. Distribution of these major genotypes was similar in both study arms. Emergence of ST3081 and concomitant disappearance of ST618 may suggest a change in the molecular epidemiology of pneumococcal serotype 1 in this region. This change is not likely to be associated with the introduction of PCV-7 which lacks serotype 1, as it was observed simultaneously in both study arms. Future population-based epidemiological studies will provide further evidence of substantive changes in the pneumococcal serotype 1 epidemiology and the likely mechanisms

Nasopharyngeal carriage of pneumococci four years after community-wide vaccination with PCV-7 in The Gambia: long-term evaluation of a cluster randomized trial.

BACKGROUND: A village-randomized trial of a seven-valent pneumococcal-conjugate-vaccine (PCV-7) conducted in rural Gambia showed a decrease of vaccine-type (VT) and a non-significant increase in non-vaccine-type (NVT) nasopharyngeal carriage of pneumococci two years after vaccination. Here, we report findings four years after vaccination. METHODS: PCV-7 was given to all children below 30 months of age enrolled in the trial and to those born during its course in all study villages. Villages were randomized (older children and adults) to receive PCV-7 (wholly vaccinated villages) or serogroup-C-meningococcal-conjugate-vaccine (partly vaccinated villages). Cross-sectional surveys (CSS) to collect nasopharyngeal swabs were conducted before and at various intervals after vaccination. Sixteen of these randomized villages (8 wholly vaccinated and 8 partly vaccinated) participated in a CSS conducted four years after vaccination started. RESULTS: Four years after vaccination, the prevalence of VT pneumococcal carriage was slightly higher in partly than in wholly vaccinated villages [6.4% versus 3.9% (p = 0.120)] compared to 24.4% in the pre-vaccination CSS (p<0.001). Prevalence of NVT four years after vaccination was similar between study groups [32.7% versus 29.8% (p = 0.392), respectively] compared to 51.1% in the pre-vaccination CSS (p<0.001). Four years after vaccination started, lower prevalence of serotype 6A was detected in wholly vaccinated than in partly vaccinated villages (1.6% versus 3.5%, p = 0.093) whilst the prevalence of serotype 19A was similar between groups (2.9% versus 2.5%, p = 0.779). The most prevalent serotype 19A clone was ST 847. The most prevalent serotype 6A clone before vaccination was ST3324 whilst after vaccination ST913 and ST1737 predominated. Fourteen out of 26 STs detected among the serotype 6A isolates were new while no new 19A serotype ST was found. CONCLUSIONS: The decline in prevalence of VT pneumococci seen shortly after PCV-7 vaccination was sustained four years later with only a small difference between study arms. No significant serotype replacement was detected. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN51695599

The impact of childhood vaccines on bacterial carriage in the nasopharynx: a longitudinal study.

BACKGROUND: There is increasing evidence that childhood vaccines have effects that extend beyond their target disease. The objective of this study was to assess the effects of routine childhood vaccines on bacterial carriage in the nasopharynx. METHODS: A cohort of children from rural Gambia was recruited at birth and followed up for one year. Nasopharyngeal swabs were taken immediately after birth, every two weeks for the first six months and then every other month. The presence of bacteria in the nasopharynx (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) was compared before and after the administration of DTP-Hib-HepB and measles-yellow fever vaccines. RESULTS: A total of 1,779 nasopharyngeal swabs were collected from 136 children for whom vaccination data were available. The prevalence of bacterial carriage was high: 82.2% S. pneumoniae, 30.6%, S.aureus, 27.8% H. influenzae. Carriage of H. influenzae (OR = 0.36; 95% CI: 0.13, 0.99) and S. pneumoniae (OR = 0.25; 95% CI: 0.07, 0.90) were significantly reduced after measles-yellow fever vaccination; while DTP-Hib-HepB had no effect on bacterial carriage. CONCLUSIONS: Nasopharyngeal bacterial carriage is unaffected by DTP-Hib-HepB vaccination and reduced after measles-yellow fever vaccination

Age and sex distribution of participants in five CSS undertaken in partly and wholly vaccinated villages.

<p>Age and sex distribution of participants in five CSS undertaken in partly and wholly vaccinated villages.</p

Comparison of prevalence of nasopharyngeal carriage of any pneumococcal carriage (Any type), vaccine serotypes (VT), non-vaccine serotypes (NVT) and serotypes 6A and 19A in different cross-sectional surveys in partly vaccinated villages.

a<p>It was not possible to fit the model.</p><p>OR's were calculated ignoring clustering and p-values using Fisher's exact test.</p

Distribution of Sequence Types (ST) of 43 serotype 19A pneumococcal isolates randomly selected from the different CSS surveys.

<p>Distribution of Sequence Types (ST) of 43 serotype 19A pneumococcal isolates randomly selected from the different CSS surveys.</p

Trial profile.

<p>PCV-7: 7-valent pneumococcal conjugate vaccine; CSS-1: Cross-sectional 1; CSS-2: Cross-sectional 2; CSS-3: Cross-sectional 3; CSS-4: Cross-sectional 4.</p

Distribution of Sequence Types (ST) of 55 serotype 6A pneumococcal isolates randomly selected from the different CSS surveys.

*<p>New Sequence Types described in this study. For the 13 new ST in the post-vaccination period, 7 come from samples collected in vaccinated villages and 6 from control villages (2 of them from PCV-7 vaccinated children).</p

Comparison of prevalence of nasopharyngeal carriage of any pneumococcal carriage (Any type), vaccine serotypes (VT), non-vaccine serotypes (NVT) and serotypes 6A and 19A in different cross-sectional surveys in wholly vaccinated villages.

a<p>It was not possible to fit the model. OR's were calculated ignoring clustering and p-values using Fisher's exact test.</p>b<p>Values could not be calculated.</p

Prevalence of pneumococcal carriage of serotypes 6A (VT group) and 19A (NVT group) in cross-sectional surveys before and after vaccination with PCV-7 stratified by age group and study arm (solid lines indicate partly vaccinated villages and dashed lines indicate wholly vaccinated villages).

<p>Prevalence of pneumococcal carriage of serotypes 6A (VT group) and 19A (NVT group) in cross-sectional surveys before and after vaccination with PCV-7 stratified by age group and study arm (solid lines indicate partly vaccinated villages and dashed lines indicate wholly vaccinated villages).</p