Pneumococcal sequence type replacement among American Indian children: A comparison of pre- and routine-PCV7 eras

Center for American Indian Health, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 621N. Washington Street, Baltimore, MD 21205, United States.
Vaccine (Impact Factor: 3.62). 11/2011; 30(13):2376-81. DOI: 10.1016/j.vaccine.2011.11.004
Source: PubMed


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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    • "In fact, 19A replacement occurred rapidly following high vaccine coverage. Initially, the majority of 19A in both carriage and disease were the result of the clonal expansion of one genotype, ST 199, already common prior to the introduction of PCV7 (Beall et al., 2011; Moore et al., 2008; Pai et al., 2005; Scott et al., 2012a). However, in time multiple unrelated genotypes were also found in increasing numbers, some of which exhibited highlevel resistance to multiple antibiotics, as in the case of the globally successful ST 320 (Clarke et al., 2004). "
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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.
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    • "The lack of description of this limitation in the literature is evidenced by the prevalence of recent studies only referencing the original primers, and not providing any discussion pertaining to the sequencing challenge [6,14-18]. The purpose of this study is to systematically identify the primers unable to obtain the correct sequence, describe an alternative set of primers, and introduce documentation to the literature offering additional guidance to groups undertaking S. pneumoniae MLST studies. "
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