Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Group A streptococci (GAS) are genetically diverse. Determination of strain features can reveal associations with disease and resistance and assist in vaccine formulation. We employed whole-genome sequence (WGS)-based characterization of 1,454 invasive GAS isolates recovered in 2015 by Active Bacterial Core Surveillance and performed conventional antimicrobial susceptibility testing. Predictions were made for genotype, GAS carbohydrate, antimicrobial resistance, surface proteins (M family, fibronectin binding, T, R28), secreted virulence proteins (Sda1, Sic, exotoxins), hyaluronate capsule, and an upregulated nga operon (encodes NADase and streptolysin O) promoter (Pnga3). Sixty-four M protein gene (emm) types were identified among 69 clonal complexes (CCs), including one CC of Streptococcus dysgalactiae subsp. equisimilis. emm types predicted the presence or absence of active sof determinants and were segregated into sof-positive or sof-negative genetic complexes. Only one “emm type switch” between strains was apparent. sof-negative strains showed a propensity to cause infections in the first quarter of the year, while sof+ strain infections were more likely in summer. Of 1,454 isolates, 808 (55.6%) were Pnga3 positive and 637 (78.9%) were accounted for by types emm1, emm89, and emm12. Theoretical coverage of a 30-valent M vaccine combined with an M-related protein (Mrp) vaccine encompassed 98% of the isolates. WGS data predicted that 15.3, 13.8, 12.7, and 0.6% of the isolates were nonsusceptible to tetracycline, erythromycin plus clindamycin, erythromycin, and fluoroquinolones, respectively, with only 19 discordant phenotypic results. Close phylogenetic clustering of emm59 isolates was consistent with recent regional emergence. This study revealed strain traits informative for GAS disease incidence tracking, outbreak detection, vaccine strategy, and antimicrobial therapy

Nasopharyngeal Carriage and Transmission of <i>Streptococcus pneumoniae</i> in American Indian Households after a Decade of Pneumococcal Conjugate Vaccine Use

<div><p>Background</p><p>Young children played a major role in pneumococcal nasopharyngeal carriage, acquisition, and transmission in the era before pneumococcal conjugate vaccine (PCV) use. Few studies document pneumococcal household dynamics in the routine-PCV7 era.</p><p>Methods</p><p>We investigated age-specific acquisition, household introduction, carriage clearance, and intra-household transmission in a prospective, longitudinal, observational cohort study of pneumococcal nasopharyngeal carriage in 300 American Indian households comprising 1,072 participants between March 2006 and March 2008.</p><p>Results</p><p>Pneumococcal acquisition rates were 2–6 times higher in children than adults. More household introductions of new pneumococcal strains were attributable to children <9 years than adults ≥17 years (p<0.001), and older children (2–8 years) than younger children (<2 years) (p<0.008). Compared to children <2 years, carriage clearance was more rapid in older children (2–4 years, HR_clearance 1.53 [95% CI: 1.22, 1.91]; 5–8 years, HR_clearance 1.71 [1.36, 2.15]) and adults (HR_clearance 1.75 [1.16, 2.64]). Exposure to serotype-specific carriage in older children (2–8 years) most consistently increased the odds of subsequently acquiring that serotype for other household members.</p><p>Conclusions</p><p>In this community with a high burden of pneumococcal colonization and disease and routine PCV7 use, children (particularly older children 2–8 years) drive intra-household pneumococcal transmission: first, by acquiring, introducing, and harboring pneumococcus within the household, and then by transmitting acquired serotypes more efficiently than household members of other ages.</p></div

Risk factors for pneumococcal acquisition (Poisson regression).

<p>^a Reported at least once during the study. Daycare defined as ≥4 hours/week outside of home with ≥2 members of other families.</p><p>^b From chart review; all other covariates ascertained via interview.</p><p>^c All models adjusted for month of study entry as a categorical variable.</p><p>^d Estimates additionally adjusted for # persons in household, crowding (number of persons per sleeping room), presence of smoker, presence of wood burning stove, and presence of running water in house. None of the other variables examined had a significant association with either individual or household carriage.</p

Adjusted number of pneumococcal acquisition events, by age category.

<p>Each point represents the mean number of individual acquisitions or household introduction for an individual in a given age category (with 95% confidence interval) over the course of the study, adjusted by all other covariates in the Poisson models set to their means.</p

Summary of pneumococcal acquisition events by age category.

<p>^a Including 73 swabs for which two serotypes were identified.</p><p>^b New acquisitions defined as acquisition of serotype not previously carried; reacquisition defined as acquisition of a previously-carried serotype.</p><p>^c Household introductions classified as “unique” if the participant was the only one in the family to acquire the new serotype; “concurrent” if more than one individual acquired the serotype simultaneously.</p

Characteristics of individuals and households enrolled in the study.

<p>^a Daycare attendance was defined as ≥4 hours per week outside the home with 2 or more children from other households.</p><p>^b Includes one child 10 years of age.</p><p>^c Includes two parents <17 years.</p><p>^d An additional 4 children <9 years of age reported receipt of PS23.</p

Intra-household pneumococcal transmission (multilevel logistic regression.

<p>^a Exposure defined as carriage of the target serotype in at least one household member in the specified age range at the previous visit.</p><p>^b Both child recipient and adult recipient models adjusted for seasonality (using the first two pairs of a truncated Fourier series), recipient characteristics (age, sex) and household characteristics (number of children <6 y, wood- or coal-burning indoor stove, and running water). Child recipient models also adjusted for vaccination status (defined as at least 3 doses of PCV7), and breastfeeding status (since last visit). Low PS23 coverage in adult age groups and the rarity of serotype-specific adult-to-adult exposure precluded the addition of PS23 vaccination status and exposure to carriage in adults ≥17 years to the adult model. Visits in which adults 17 years were exposed to carriage in another adult ≥17 years at the previous visit were excluded from the adult model.</p