Invasive Group A Streptococcal Infections in 10 US States.

Importance: Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity, mortality, and economic burden.

Objective: To update trends in invasive GAS disease incidence rates in 10 US states between 2013 and 2022.

Design, Setting, And Participants: Clinical, demographic, and laboratory data for invasive GAS cases were collected as part of population-based surveillance in the Active Bacterial Core surveillance network covering 34.

Update on the evolving landscape of pneumococcal capsule types: new discoveries and way forward.

SUMMARY (the "pneumococcus") is a significant human pathogen. The key determinant of pneumococcal fitness and virulence is its ability to produce a protective polysaccharide (PS) capsule, and anti-capsule antibodies mediate serotype-specific opsonophagocytic killing of bacteria. Notably, immunization with pneumococcal conjugate vaccines (PCVs) has effectively reduced the burden of disease caused by serotypes included in vaccines but has also spurred a relative upsurge in the prevalence of non-vaccine serotypes.

Genomic cluster formation among invasive group A streptococcal infections in the USA: a whole-genome sequencing and population-based surveillance study.

Background: Clusters of invasive group A streptococcal (iGAS) infection, linked to genomically closely related group A streptococcal (GAS) isolates (referred to as genomic clusters), pose public health threats, and are increasingly identified through whole-genome sequencing (WGS) analysis. In this study, we aimed to assess the risk of genomic cluster formation among iGAS cases not already part of existing genomic clusters.

Methods: In this WGS and population-based surveillance study, we analysed iGAS case isolates from the Active Bacterial Core surveillance (ABCs), which is part of the US Centers for Disease Control and Prevention's Emerging Infections Program, in ten US states from Jan 1, 2015, to Dec 31, 2019.

Recombinational exchange of M-fibril and T-pilus genes generates extensive cell surface diversity in the global group A population.

Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with typing, provides an account of the global GAS strain population. Cluster analysis based on nucleotide sequence similarity assigns most T-serotypes to discrete pilin backbone sequence clusters, yet the established T-types correspond to only half the clusters.

Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S.

A novel invasive Streptococcus pyogenes variant sublineage derived through recombinational replacement of the emm12 genomic region.

Group A streptococcal strains potentially acquire new M protein gene types through genetic recombination (emm switching). To detect such variants, we screened 12,596 invasive GAS genomes for strains of differing emm types that shared the same multilocus sequence type (ST). Through this screening we detected a variant consisting of 16 serum opacity factor (SOF)-positive, emm pattern E, emm82 isolates that were ST36, previously only associated with SOF-negative, emm pattern A, emm12.

Variation in pneumococcal invasiveness metrics is driven by serotype carriage duration and initial risk of disease.

Streptococcus pneumoniae is an opportunistic pathogen that, while usually carried asymptomatically, can cause severe invasive diseases like meningitis and bacteremic pneumonia. A central goal in S. pneumoniae public health management is to identify which serotypes (immunologically distinct strains) pose the most risk of invasive disease.

Expansion of Invasive Group A Streptococcus M1 Lineage in Active Bacterial Core Surveillance, United States, 2019‒2021.

From 2015-2018 to 2019‒2021, hypertoxigenic M1 lineage among invasive group A Streptococcus increased in the United States (1.7%, 21/1,230 to 11%, 65/603; p<0.001).

Invasive Group A Streptococcal Penicillin Binding Protein 2× Variants Associated with Reduced Susceptibility to β-Lactam Antibiotics in the United States, 2015-2021.

All known group A streptococci [GAS] are susceptible to β-lactam antibiotics. We recently identified an invasive GAS (iGAS) variant (/PBP2x-T553K) with unusually high minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin, although clinically susceptible to β-lactams. We aimed to quantitate PBP2x variants, small changes in β-lactam MICs, and lineages within contemporary population-based iGAS.

Continued Increase of Erythromycin Nonsusceptibility and Clindamycin Nonsusceptibility Among Invasive Group A Streptococci Driven by Genomic Clusters, United States, 2018-2019.

We analyzed 9630 invasive GAS surveillance isolates in the USA. From 2015-2017 to 2018-2019, significant increases in erythromycin-nonsusceptibility (18% vs 25%) and clindamycin-nonsusceptibility (17% vs 24%) occurred, driven by rapid expansions of genomic subclones. Prevention and control of clustered infections appear key to containing antimicrobial resistance.

Cluster Transmission Drives Invasive Group A Streptococcus Disease Within the United States and Is Focused on Communities Experiencing Disadvantage.

Background: Group A streptococci (GAS), although usually responsible for mild infections, can sometimes spread into normally sterile sites and cause invasive GAS disease (iGAS). Because both the risk of iGAS disease and occurrence of outbreaks are elevated within certain communities, such as those comprising people who inject drugs (PWID) and people experiencing homelessness (PEH), understanding the transmission dynamics of GAS is of major relevance to public health.

Methods: We used a cluster detection tool to scan genomes of 7552 Streptococcus pyogenes isolates acquired through the population-based Active Bacterial Core surveillance (ABCs) during 2015-2018 to identify genomically related clusters representing previously unidentified iGAS outbreaks.

Impact of Pneumococcal Conjugate Vaccines on Antibiotic-Nonsusceptible Invasive Pneumococcal Disease in the United States.

Background: Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States after introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD.

Methods: We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018.

A lineage usually associated with pneumococcal conjugate vaccine (PCV) serotypes is the most common cause of serotype 35B invasive disease in South Africa, following routine use of PCV.

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction.

Invasive Pneumococcal Disease Clusters Disproportionally Impact Persons Experiencing Homelessness, Injecting Drug Users, and the Western United States.

Background: Invasive pneumococcal disease (IPD) isolates forming genomic clusters can reflect rapid disease transmission between vulnerable individuals.

Methods: We performed whole genome sequencing of 2820 IPD isolates recovered during 2019 through Centers for Disease Control and Prevention's Active Bacterial Core surveillance to provide strain information (serotypes, resistance, genotypes), and 2778 of these genomes were analyzed to detect highly related genomic clusters.

Results: Isolates from persons experiencing homelessness (PEH) were more often within genomic clusters than those from persons not experiencing homelessness (PNEH) (105/198 [53.

Genomic Characterization of Group A Streptococci Causing Pharyngitis and Invasive Disease in Colorado, USA, June 2016- April 2017.

Background: The genomic features and transmission link of circulating Group A Streptococcus (GAS) strains causing different disease types, such as pharyngitis and invasive disease, are not well understood.

Methods: We used whole-genome sequencing to characterize GAS isolates recovered from persons with pharyngitis and invasive disease in the Denver metropolitan area from June 2016 to April 2017.

Results: The GAS isolates were cultured from 236 invasive and 417 pharyngitis infections.

serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from .

is an important global pathogen that causes bacterial pneumonia, sepsis and meningitis. Beta-lactam antibiotics are the first-line treatment for pneumococcal disease, however, their effectiveness is hampered by beta-lactam resistance facilitated by horizontal genetic transfer (HGT) with closely related species. Although interspecies HGT is known to occur among the species of the genus , the rates and effects of HGT between and its close relatives involving the penicillin binding protein () genes remain poorly understood.

Triplex Direct Quantitative Polymerase Chain Reaction for the Identification of Streptococcus pneumoniae Serotypes.

The quantitative polymerase chain reaction (qPCR) method presented in this study allows the identification of pneumococcal capsular serotypes in cerebrospinal fluid without first performing DNA extraction. This testing approach, which saves time and resources, demonstrated similar sensitivity and a high level of agreement between cycle threshold values when it was compared side-by-side with the standard qPCR method with extracted DNA.

The role of interspecies recombination in the evolution of antibiotic-resistant pneumococci.

Multidrug-resistant emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance.

Patterns of Antibiotic Nonsusceptibility Among Invasive Group A Streptococcus Infections-United States, 2006-2017.

Background: Treatment of severe group A Streptococcus (GAS) infections requires timely and appropriate antibiotic therapy. We describe the epidemiology of antimicrobial-resistant invasive GAS (iGAS) infections in the United States (US).

Methods: We analyzed population-based iGAS surveillance data at 10 US sites from 2006 through 2017.

Nonpneumococcal Strains Recently Recovered from Carriage Specimens and Expressing Capsular Serotypes Highly Related or Identical to Pneumococcal Serotypes 2, 4, 9A, 13, and 23A.

The polysaccharide capsule is a key virulence factor of There are numerous epidemiologically important pneumococcal capsular serotypes, and recent findings have demonstrated that several of them are commonly found among nonpathogenic commensal species. Here, we describe 9 nonpneumococcal strains carrying close homologs of pneumococcal capsular biosynthetic () loci that were discovered during recent pneumococcal carriage studies of adults in the United States and Kenya. Two distinct strains cross-reactive with pneumococcal serotype 4 and carrying -like capsular biosynthetic () loci were recovered.

Serotype-Switch Variant of Multidrug-Resistant Streptococcus pneumoniae Sequence Type 271.

We discovered 3 invasive, multidrug-resistant Streptococcus pneumoniae isolates of vaccine-refractory capsular serotype 3 that recently arose within the successful sequence type 271 complex through a serotype switch recombination event. Mapping genomic recombination sites within the serotype 3/sequence type 271 progeny revealed a 55.9-kb donated fragment that encompassed cps3, pbp1a, and additional virulence factors.