Pneumococcal sequence type replacement among American Indian children: A comparison of pre- and routine-PCV7 eras
ABSTRACT Multi-locus sequence typing (MLST) of pneumococcal isolates collected during an efficacy trial of the 7-valent pneumococcal conjugate vaccine (PCV7) among Navajo and White Mountain Apache children from 1998 to 2000 showed a non-differential expansion of pre-existing sequence types (STs) and only one capsule-switching event in the PCV7-randomized communities. PCV7 was introduced as a routine infant vaccine in October 2000. We assessed variability in PCV7 effectiveness and mechanisms of ST replacement after prolonged routine PCV7 use.
We applied MLST to 267 non-vaccine type pneumococcal carriage and invasive disease isolates from Navajo and White Mountain Apache children from 2006 to 2008, and compared them to those from 1998 to 2000. Microarray was used to confirm capsule switching events.
The primary mechanism of ST replacement among Navajo and White Mountain Apache children was expansion of existing STs, although introduction of new STs was an important secondary mechanism. ST199, a majority being serotype 19A, was the most common ST in both eras. Only ST193 (serotype 21) was preferentially expanding in the PCV7 era. Three examples of capsule switching were identified. No variability in vaccine effectiveness by ST was observed.
We did not observe an influence of ST on PCV7 serotype-specific effectiveness, although some STs may be favored in replacement.
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ABSTRACT: SUMMARY The major evolutionary stresses on Streptococcus pneumoniae are thought to be the widespread use of antibiotics and the deployment of effective vaccines against the capsular polysaccharides. Our current knowledge of genetic lineages among pneumococcal isolates comes largely from investigations just before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) introduced in 2000. We examined 66 serogroup 6 isolates from the 1970s, long before the introduction of PCV7 and before widespread penicillin resistance was common in Birmingham, Alabama, to look for ancestors of the clones that came into play around the introduction of the PCV7 vaccine. The hypothesis was that some clonal complexes, if not individual clones, would be stable enough to persist over this period of time. We compared the 1970s isolates with 122 isolates from the 1990s in US and worldwide collections. Genotyping with pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) revealed that while some clones were probably localized to our area, others have persisted within groups that have expanded or diminished over the years.Epidemiology and Infection 03/2014; DOI:10.1017/S0950268814000508 · 2.49 Impact Factor
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ABSTRACT: Background Multi-locus sequence typing (MLST) is a portable, broadly applicable method for classifying bacterial isolates at an intra-species level. This methodology provides clinical and scientific investigators with a standardized means of monitoring evolution within bacterial populations. MLST uses the DNA sequences from a set of genes such that each unique combination of sequences defines an isolate’s sequence type. In order to reliably determine the sequence of a typing gene, matching sequence reads for both strands of the gene must be obtained. This study assesses the ability of both the standard, and an alternative set of, Streptococcus pneumoniae MLST primers to completely sequence, in both directions, the required typing alleles. Results The results demonstrated that for five (aroE, recP, spi, xpt, ddl) of the seven S. pneumoniae typing alleles, the standard primers were unable to obtain the complete forward and reverse sequences. This is due to the standard primers annealing too closely to the target regions, and current sequencing technology failing to sequence the bases that are too close to the primer. The alternative primer set described here, which includes a combination of primers proposed by the CDC and several designed as part of this study, addresses this limitation by annealing to highly conserved segments further from the target region. This primer set was subsequently employed to sequence type 105 S. pneumoniae isolates collected by the Canadian Immunization Monitoring Program ACTive (IMPACT) over a period of 18 years. Conclusions The inability of several of the standard S. pneumoniae MLST primers to fully sequence the required region was consistently observed and is the result of a shift in sequencing technology occurring after the original primers were designed. The results presented here introduce clear documentation describing this phenomenon into the literature, and provide additional guidance, through the introduction of a widely validated set of alternative primers, to research groups seeking to undertake S. pneumoniae MLST based studies.BMC Microbiology 06/2014; 14(1):143. DOI:10.1186/1471-2180-14-143 · 2.98 Impact Factor
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ABSTRACT: The genus Streptococcus contains 104 recognized species, many of which are associated with human or animal hosts. A globally prevalent human pathogen in this group is Streptococcus pneumoniae (the pneumococcus). While being a common resident of the upper respiratory tract, it is also a major cause of otitis media, pneumonia, bacteremia and meningitis, accounting for a high burden of morbidity and mortality worldwide. Recent findings demonstrate the importance of recombination and selection in driving the population dynamics and evolution of different pneumococcal lineages, allowing them to successfully evade the impacts of selective pressures such as vaccination and antibiotic treatment. We highlight the ability of pneumococci to respond to these pressures through processes including serotype replacement, capsular switching and horizontal gene transfer (HGT) of antibiotic resistance genes. The challenge in controlling this pathogen also lies in the exceptional genetic and phenotypic variation among different pneumococcal lineages, particularly in terms of their pathogenicity and resistance to current therapeutic strategies. The widespread use of pneumococcal conjugate vaccines, which target only a small subset of the more than 90 pneumococcal serotypes, provides us with a unique opportunity to elucidate how the processes of selection and recombination interact to generate a remarkable level of plasticity and heterogeneity in the pneumococcal genome. These processes also play an important role in the emergence and spread of multi-resistant strains, which continues to pose a challenge in disease control and/or eradication. The application of population of genomic approaches at different spatial and temporal scales will help improve strategies to control this global pathogen, and potentially other pathogenic streptococci.Infection Genetics and Evolution 11/2014; DOI:10.1016/j.meegid.2014.11.007 · 3.26 Impact Factor