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Emerging invasive pneumococcal serotype not covered by vaccine
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Researchers are concerned about the emergence of an invasive pneumococcal serotype that is not covered by the conjugate vaccine.
CDC researchers analyzed recent government surveillance data and found nearly 200 strains belonging to nonvaccine serotype 35B, which they said has emerged in the U.S. as an increasing cause of penicillin-resistant invasive pneumococcal disease (IPD) and should be considered for inclusion in future vaccines.
“This finding is of concern because even strains that are rarely detected in IPD sometimes rapidly emerge,” the researchers wrote in an Emerging Infectious Diseases report released today.
They used whole-genome sequencing to characterize more than 4,200 pneumococcal strains from the CDC’s population-based Active Bacterial Core surveillance (ABCs) program, which covers approximately 32 million people in 10 states. According to their report, the effectiveness of pneumococcal conjugate vaccines has been hampered over the years by emergent serotypes like 35B.
For the study, the researchers analyzed data on pneumococcal strains that caused IPD in the U.S. in 2015 and 2016, including 199 strains of 35B, and compared the results with previous data from the ABCs program. According to the findings, IPD caused by strains from the 35B serotype increased after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, then increased even further after the 13-valent conjugate vaccine (PCV13) debuted in 2010.
The researchers uncovered several 35B variants that were generated by capsular switch events, including one that involved the 35B/sequence type (ST) 558 lineage — the primary contributor to post–PCV13 antimicrobial-resistant 35B IPD — and vaccine serotype 9V/ST156. The resulting strain, 35B/ST156, was identified in six states in 2015 and 2016.
The researchers characterized the emergence of 35B/ST156 as a “cause for concern” because the ST156 genotype has a history of evading conjugate vaccines. They said 35B has become the predominant serotype of the ST156 lineage since the introduction of PCV13. Previously, 19A was the predominant serotype of the ST156 lineage between its emergence after the introduction of PCV7 and its addition to PCV13.
“Serotype 35B strains have several of the same features that were found among serotype 19A strains before implementation of PCV7 in 2000,” the researchers wrote. “These features that could predispose for serotype 35B to continue its increasing trend as a cause of IPD include its lack of inclusion within conjugate vaccine, high carriage rates within children, antimicrobial resistance, clonal expansion, and serotype switching.”
In addition to strains from 35B, the researchers identified other pneumococcal serotypes that have increasingly or commonly caused IPD and further complicate the composition of more encompassing vaccines. – by Gerard Gallagher
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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The CDC released data indicating that an antibiotic-resistant invasive serotype of Streptococcus pneumoniae, 35B, was expanding in number and distribution in the United States over the period 2015-2016. As part of its routine efforts to monitor pneumococcal serotypes, the CDC collects isolates causing invasive pneumococcal disease from sentinel sites throughout the country.
Widespread pneumococcal vaccination of young children with PCV7 beginning in 2000 and with PCV13 since 2010 has markedly reduced pneumococcal disease caused by vaccine serotypes. The CDC used whole genome sequencing to study the new 35B strain and determined that the strain had actually arisen from a 9V strain that had simply switched its capsule from the 9V vaccine serotype to a nonvaccine serotype 35B while retaining virulence genes, including antibiotic resistance features, associated with the original 9V strain. The conjugate vaccines have been extremely successful in providing protection against the capsular serotypes included in the PCV7 and PCV13 vaccines. However, the 35B serotype is not contained in the conjugate vaccines and appears to be emerging as an important nonvaccine serotype.
There are several features that could contribute to the increasing prevalence of 35B strains. These include biological pressure induced by the conjugate pneumococcal vaccines; high carriage rates in children; antibiotic use; clonal expansion; and serotype switching. The use of whole-genome sequencing to characterize invasive pneumococcal isolates should continue to provide direction on what additional serotypes should be considered for inclusion in future pneumococcal conjugate vaccines.
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