Serological responses to target Streptococcus pyogenes vaccine antigens in patients with proven invasive beta-haemolytic streptococcal infections.

BACKGROUND: Rising incidence of invasive beta-haemolytic streptococcal (iBHS) infections has prompted consideration of vaccination as a preventative strategy for at-risk populations. The benefits of a vaccine targeting Lancefield group A (Streptococcus pyogenes; Strep A) would increase if cross-species immunity against Lancefield groups C/G (Streptococcus dysgalactiae subspecies equisimilis; SDSE) and B (Streptococcus agalactiae; GBS) was demonstrated. METHODS: A prospective, observational study of adult patients with iBHS infections due to Strep A, SDSE or GBS. Antibody responses to six Strep A candidate antigens were assayed on acute and convalescent sera. A serological response was defined as an increase of >0.2log10 arbitrary units/mL (AU/mL). RESULTS: Sixty-seven participants were enrolled. Thirty-three participants were included in the final analysis (12, 11 and 10 with Strep A, SDSE and GBS, respectively). The median serological response for participants with Strep A was significant for all tested antigens (median >0.2log10 difference between acute and convalescent samples; P<0.05 for all). Those with SDSE had comparable and significant median (IQR) responses to streptolysin-O (0.65 [0.36-1.67], P=0.004), S. pyogenes adhesion and division protein (0.68 [0.36-1.63], P=0.005) and C5a peptidase (ScpA; 0.30 [0.23-1.06]), P=0.004). GBS responses were limited to ScpA only (0.34 [0.08-0.52], P=0.05). CONCLUSION: Patients with invasive Strep A infection mount robust antibody responses to six non-M protein vaccine candidate antigens. Similar significant responses to C5a peptidase in those with invasive SDSE and GBS infection highlight the importance of further research into cross-species protection and immunological correlates of vaccine efficacy.

Clonal Expansion of Multidrug-Resistant Streptococcus dysgalactiae Subspecies equisimilis Causing Bacteremia, Japan, 2005-2021.

Incidence of Streptococcus dysgalactiae subspecies equisimilis (SDSE) bacteremia is increasing in the Kyoto-Shiga region of Japan. We retrospectively analyzed clinical features of SDSE bacteremia and conducted comparative genomic analyses of isolates collected from 146 bacteremia episodes among 133 patients during 2005-2021. Of those patients, 7.7% required vasopressor support, and 7.0% died while in the hospital. The prevalence of isolates resistant to erythromycin, minocycline, and clindamycin increased from 8.6% during 2005-2017 to 21.6% during 2018-2021. Our genomic analysis demonstrated that sequence type 525 and clonal complex 25 were predominant in SDSE isolates collected during 2018-2021. In addition, those isolates had acquired 2 antimicrobial-resistance genes, ermB and tetM, via Tn916-like integrative and conjugative elements (ICEs). Phylogenetic analysis revealed clonal distribution of Tn916-like ICEs in SDSE isolates. Our findings suggest that Tn916-like ICEs contributed to the emergence and recent increase of multidrug-resistant SDSE bacteremia in this region of Japan.

Incidence, seasonal pattern, and clinical manifestations of Streptococcus dysgalactiae subspecies equisimilis bacteremia; a population-based study.

Streptococcus dysgalactiae subspecies equisimilis (SDSE) is a human pathogen causing severe invasive infections. Population-based studies on SDSE bacteremia are limited. The purpose of this study was to investigate the incidence, seasonal pattern, clinical manifestations, and recurrence of SDSE bacteraemia. Records regarding patients aged ≥ 18 years with SDSE bacteremia in the Pirkanmaa health district in August 2015 to July 2018 were retrospectively reviewed. A total of 230 SDSE bacteremia episodes were identified, with 217 episodes (involving 211 patients) available for analysis. The mean annual incidence rate of SDSE bacteremia was 16.9/100 000 inhabitants. Most episodes (33%) were detected in the summer (June to August) (p = 0.058). Episodes with bacteremic cellulitis were statistically significantly more common during the summer compared with other seasons (p = 0.008). Cellulitis was the most common presenting clinical manifestation of SDSE bacteremia (68% of all episodes). Risk factors of recurring bacteremia were chronic eczema and/or skin erosion (OR 3.96 [95% CI 1.11-14.1]), heart disease (OR 3.56 [95% CI 1.22-10.4]), diabetes (OR 3.77 [95% CI 1.35-10.5]) and a history of cellulitis. We found a remarkably high incidence of SDSE bacteraemia in the Pirkanmaa health district. Bacteraemic cellulitis, which was the predominant clinical manifestation is more often occurred in the summer. Risk factors of recurring SDSE bacteremia were a history of cellulitis, chronic eczema or skin erosion, diabetes, and heart disease.

Major risk factors for Streptococcus dysgalactiae subsp. equisimilis bacteremia: a population-based study.

BACKGROUND: Streptococcus dysgalactiae subspecies equisimilis is a human pathogen causing severe invasive infections. Detailed information on S. dysgalactiae subsp. equisimilis bacteremia and especially of predisposing factors are lacking. The purpose of the study is to investigate the risk factors of S. dysgalactiae subsp. equisimilis bacteremia compared to the general population in Finland. METHODS: We retrospectively reviewed all patients older than 18 years with S. dysgalactiae subsp. equisimilis bacteremia in the Pirkanmaa health district from August 2015 to July 2018. The risk factors for S. dysgalactiae subsp. equisimilis bacteremia were investigated with respect to the normal population in Finland using the Finhealth study data provided by the Finnish institute for health and welfare. The study group was matched with the Finhealth study by age and sex. RESULTS: Altogether 230 cases of S. dysgalactiae subsp. equisimilis bacteremia were detected. The medical records of 217 episodes of S. dysgalactiae subsp. equisimilis bacteremia (involving 211 patients) were available for analysis. Obesity was a statistically significant risk factor for S. dysgalactiae subsp. equisimilis bacteremia (Odds Ratio 2.96 [95% CI 2.22-3.96]). Diabetes and coronary artery disease were also associated with an increased risk of S. dysgalactiae subsp. equisimilis bacteremia (OR 4.82 [95% CI 3.62-6.42]) and (OR 3.03 [95% CI 2.18-4.19]). CONCLUSIONS: We found obesity, diabetes, and coronary artery disease to be associated with an increased risk for S. dysgalactiae subsp. equisimilis bacteremia. These results provide an increased understanding of risk factors for S. dysgalactiae subsp. equisimilis bacteremia.

Characterization of an experimental model to determine streptococcal M protein-induced autoimmune cardiac and neurobehavioral abnormalities.

Group A streptococcal (GAS) infection is associated with a spectrum of autoimmune diseases including acute rheumatic fever/rheumatic heart disease (ARF/RHD) and neurobehavioral abnormalities. Antibodies against GAS M proteins cross-react with host tissue proteins in the heart and brain leading to the symptomatology observed in ARF/RHD. As throat carriage of Streptococcus dysgalactiae subspecies equisimilis (SDSE) has been reported to be relatively high in some ARF/RHD endemic regions compared with GAS, and both SDSE and GAS express coiled-coil surface protein called M protein, we hypothesized that streptococci other than GAS can also associated with ARF/RHD and neurobehavioral abnormalities. Neurobehavioral assessments and electrocardiography were performed on Lewis rats before and after exposure to recombinant GAS and SDSE M proteins. Histological assessments were performed to confirm inflammatory changes in cardiac and neuronal tissues. ELISA and Western blot analysis were performed to determine the cross-reactivity of antibodies with host connective, cardiac and neuronal tissue proteins. Lewis rats injected with M proteins either from GAS or SDSE developed significant cardiac functional and neurobehavioral abnormalities in comparison to control rats injected with phosphate-buffered saline. Antibodies against GAS and SDSE M proteins cross-reacted with cardiac, connective and neuronal proteins. Serum from rats injected with streptococcal antigens showed higher immunoglobulin G binding to the striatum and cortex of the brain. Cardiac and neurobehavioral abnormalities observed in our experimental model were comparable to the cardinal symptoms observed in patients with ARF/RHD. Here for the first time, we demonstrate in an experimental model that M proteins from different streptococcal species could initiate and drive the autoimmune-mediated cardiac tissue damage and neurobehavioral abnormalities.

Impact of intra-partum azithromycin on carriage of group A streptococcus in the Gambia: a posthoc analysis of a double-blind randomized placebo-controlled trial.

BACKGROUND: Group A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis. Asymptomatic bacterial colonization is considered a necessary step towards sepsis. Intra-partum azithromycin may reduce GAS carriage. METHODS: A posthoc analysis of a double-blind, placebo-controlled randomized-trial was performed to determine the impact of 2 g oral dose of intra-partum azithromycin on maternal and neonatal GAS carriage and antibiotic resistance. Following screening, 829 mothers were randomized who delivered 843 babies. GAS was determined by obtaining samples from the maternal and newborn nasopharynx, maternal vaginal tract and breastmilk. Whole Genome Sequencing (WGS) of GAS isolates was performed using the Illumina Miseq platform. RESULTS: GAS carriage was lower in the nasopharynx of both mothers and babies and breast milk among participants in the azithromycin arm. No differences in GAS carriage were found between groups in the vaginal tract. The occurrence of azithromycin-resistant GAS was similar in both arms, except for a higher prevalence in the vaginal tract among women in the azithromycin arm. WGS revealed all macrolide-resistant vaginal tract isolates from the azithromycin arm were Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate (SDSE(A)) harbouring macrolide resistant genes msr(D) and mef(A). Ten of the 45 GAS isolates (22.2%) were SDSE(A). CONCLUSIONS: Oral intra-partum azithromycin reduced GAS carriage among Gambian mothers and neonates however carriage in the maternal vaginal tract was not affected by the intervention due to azithromycin resistant SDSE(A). SDSE(A) resistance must be closely monitored to fully assess the public health impact of intrapartum azithromycin on GAS. Trial registration ClinicalTrials.gov Identifier NCT01800942.

Pyogenic spondylitis caused by Streptococcus dysgalactiae subspecies equisimilis in a patient with nasopharyngeal cancer.

In the treatment of head and neck cancer, radiation therapy is an effective modality and is often used in routine clinical practice. Although rare, pyogenic spondylitis has been reported as a complication of radiation therapy. Here, we report a case of nasopharyngeal carcinoma resulting in pyogenic spondylitis from a catheter-related bloodstream infection after chemoradiotherapy. The initial symptoms were fever and posterior cervical pain. Streptococcus dysgalactiae subspecies equisimilis was detected in blood cultures. Magnetic resonance imaging showed abnormal enhancement of the C6 and C7 vertebrae and an anterior epidural abscess. The infection was successfully treated with antibacterial therapy.

Erythematous rash and postinfectious acral desquamation due to Streptococcus dysgalactiae subspecies equisimilis infection in a child.

Streptococcus dysgalactiae subspecies equisimilis infection is an emerging pathogen. Cutaneous and systemic manifestations resemble those of other pyogenic streptococci. However, the rapid group A antigen detection test used to diagnose Streptococcus pyogenes infection is usually negative, making the diagnosis difficult. If clinical suspicion of streptococcal infection is high, a tonsillar culture should be performed to confirm the diagnosis.

Association between bacterial finding, antibiotic treatment and clinical course in patients with pharyngotonsillitis: a registry-based study in primary healthcare in Sweden.

BACKGROUND: The role of non-group A streptococci and Fusobacterium necrophorum in pharyngotonsillitis has been disputed and few prospective studies have evaluated the effect of antibiotic treatment. This study uses registry data to investigate the relation between antibiotic prescription for pharyngotonsillitis in primary healthcare and return visits for pharyngotonsillitis, complications, and tonsillectomy. METHODS: Retrospective data were extracted from the regional electronic medical record system in Kronoberg County, Sweden, for all patients diagnosed with pharyngotonsillitis between 2012 and 2016. From these data, two cohorts were formed: one based on rapid antigen detection tests (RADT) for group A streptococci (GAS) and one based on routine throat cultures for ß-haemolytic streptococci and F. necrophorum. The 90 days following the inclusion visit were assessed for new visits for pharyngotonsillitis, complications, and tonsillectomy, and related to bacterial aetiology and antibiotic prescriptions given at inclusion. RESULTS: In the RADT cohort (n = 13,781), antibiotic prescription for patients with a positive RADT for GAS was associated with fewer return visits for pharyngotonsillitis within 30 days compared with no prescription (8.7% vs. 12%; p = 0.02), but not with the complication rate within 30 days (1.5% vs. 1.8%; p = 0.7) or with the tonsillectomy rate within 90 days (0.27% vs. 0.26%; p = 1). In contrast, antibiotic prescription for patients with a negative RADT was associated with more return visits for pharyngotonsillitis within 30 days (9.7% vs. 7.0%; p = 0.01). In the culture cohort (n = 1 370), antibiotic prescription for patients with Streptococcus dysgalactiae ssp. equisimilis was associated with fewer return visits for pharyngotonsillitis within 30 days compared with no prescription (15% vs. 29%; p = 0.03). CONCLUSIONS: Antibiotic prescription was associated with fewer return visits for pharyngotonsillitis in patients with a positive RADT for GAS but with more return visits in patients with a negative RADT for GAS. There were no differences in purulent complications related to antibiotic prescription.

Immunoglobulin Attenuates Streptokinase-Mediated Virulence in Streptococcus dysgalactiae Subspecies equisimilis Necrotizing Fasciitis.

Background: Necrotizing fasciitis (NF) retains a very high mortality rate despite prompt and adequate antibiotic treatment and surgical debridement. Necrotizing fasciitis has recently been associated with Streptococcus dysgalactiae subspecies equisimilis (SDSE). Methods: We investigated the causes of a very severe clinical manifestation of SDSE-NF by assessing both host and pathogen factors. Results: We found a lack of streptokinase-function blocking antibodies in the patient resulting in increased streptokinase-mediated fibrinolysis and bacterial spread. At the same time, the clinical SDSE isolate produced very high levels of streptokinase. Exogenous immunoglobulin Gs (ex-IgGs) efficiently blocked streptokinase-mediated fibrinolysis in vitro, indicating a protective role against the action of streptokinase. In vivo, SDSE infection severity was also attenuated by ex-IgGs in a NF mouse model. Conclusions: These findings illustrate for the first time that the lack of specific antibodies against streptococcal virulence factors, such as streptokinase, may contribute to NF disease severity. This can be counteracted by ex-IgGs.

Exploring the arthritogenicity of Streptococcus dysgalactiae subspecies equisimilis.

BACKGROUND: During the past decades, Streptococcus dysgalactiae subspecies equisimilis (SDSE) has been increasingly recognized as an important human pathogen. Osteoarticular infections is one of the predominant disease manifestations of SDSE, but the pathogenetic rationale for its arthritogenicity has yet to be unravelled. We aimed to explore if the rising incidence of osteoarticular infections caused by this pathogen in our region emanated from clonal expansion of strains with enhanced tropism for bone and joint tissue components or orthopaedic implants. RESULTS: Twenty-nine SDSE-isolates associated with osteoarticular infections were retrospectively identified. Their genomic content and affinity for fibronectin, collagen and stainless steel were compared to 24 temporally and geographically matched SDSE blood culture isolates obtained from patients without bone or joint infections. Despite a thorough genetic and phenotypic dissection, neither the presence or absence of any single gene, nor the binding abilities of the SDSE isolates, were predictive of clinical entity. SNP analysis revealed a heterogenous population, and a correlation between phylogenetic relationships and disease manifestation was not evident. However, we identified a strong concordance between phenotypic binding abilities and genetic variations in the pilus-region, also denoted as the FCT-region (Fibronectin binding, Collagen binding and T-antigen). This observation could be related to the ample and varied repertoire of putative adhesins residing within this region, including proteins predicted to adhere to fibronectin and collagen, as well as fibrinogen. CONCLUSIONS: SDSE strains associated with osteoarticular infections do not emanate from subpopulation characterized by distinct genetic or phenotypic traits. The genetic architecture of the pilus region was predictive of the adhesive properties of the SDSE-isolates, but its role in tissue tropism needs further investigation. To the best of our knowledge, this is the first comprehensive characterization of the genetic landscape of the SDSE pilus region.

Molecular characterization and antibiotic resistance of Streptococcus dysgalactiae subspecies equisimilis isolated from patients with streptococcal toxic shock syndrome.

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multiorgan failure, and high mortality. Although STSS is mainly caused by Streptococcus pyogenes, group G streptococcus identified as S. dysgalactiae subsp. equisimilis (SDSE) causing STSS has also been reported; however, no study has analyzed >100 isolates of SDSE causing STSS. Therefore, we characterized the emm genotype of 173 SDSE isolates obtained from STSS patients in Japan during 2014-2016 and performed antimicrobial susceptibility testing using the broth microdilution method and emm gene typing. The predominant emm genotype was found to be stG6792, followed by stG485, stG245, stG10, stG6, and stG2078. These six genotypes constituted more than 75% of the STSS isolates. The proportion of each emm genotype in STSS isolates correlated with that in invasive isolates previously reported. We found that 16.2% of the isolates showed clindamycin resistance. The proportion of clindamycin-resistant SDSE isolates was significantly higher than that of S. pyogenes isolates. Thus, while treating STSS caused by SDSE, it is necessary to consider the possibility of clindamycin resistance and to ensure judicious use of the drug.

Streptococcal Toxic Shock Syndrome Caused by Streptococcus dysgalactiae subsp. equisimilis-related Empyema: A Novel Case Report.

Streptococcal toxic shock syndrome (STSS) caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE)-related empyema is rare but can result in shock vitals, acute kidney injury, and extensive erythema. In the present case, a 92-year-old woman with empyema caused by SDSE developed STSS after pleural drainage and antibiotic therapy. Despite temporary improvement with clindamycin and pleural drainage, the patient ultimately died due to malnutrition. Autopsy findings suggested that the infection was well controlled, but infections with Streptococcus spp., including SDSE, can trigger STSS in patients with empyema.

Epidemiological and Clinical Features of Streptococcus dysgalactiae ssp. equisimilis stG62647 and Other emm Types in Germany.

(1) Background: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is an important ß-hemolytic pathogen historically described as mainly affecting animals. Studies epidemiologically assessing the pathogenicity in the human population in Germany are rare. (2) Methods: the present study combines national surveillance data from 2010 to 2022 with a single-center clinical study conducted from 2016 to 2022, focusing on emm type, Lancefield antigen, antimicrobial resistance, patient characteristics, disease severity, and clinical infection markers. (3) Results: The nationwide reported invasive SDSE infections suggest an increasing infection burden for the German population. One particular emm type, stG62647, increased over the study period, being the dominant type in both study cohorts, suggesting a mutation-driven outbreak of a virulent clone. The patient data show that men were more affected than women, although in the single-center cohort, this trend was reversed for patients with stG62647 SDSE. Men affected by stG62647 developed predominantly fascial infections, whereas women suffering from superficial and fascial non-stG62647 SDSE infections were significantly younger than other patients. Increasing age was a general risk factor for invasive SDSE infections. (4) Conclusions: further studies are needed to further elucidate the raised questions regarding outbreak origin, underlying molecular mechanisms as well as sex-dependent pathogen adaptation.

Progressive Lameness of a Greater One-Horned Rhinoceros (Rhinoceros unicornis) Associated with a Retroperitoneal Abscess and Thrombus Caused by Streptococcus dysgalactiae Subspecies equisimilis.

In rhinoceroses, lameness is an occasionally seen symptom primarily caused by lesions affecting the feet and interdigital space. A 3-year-old male Greater one-horned rhinoceros developed a progressive, severe movement disorder of the right hind limb with subsequent death. The pathological analysis diagnosed a severe, retroperitoneal abscess and chronic thrombosis of the right iliac artery. Streptococci detected in the abscess were further identified as Streptococcus dysgalactiae subspecies equisimilis by culture and molecular techniques. The identical isolate was also identified in a vaginal swab of the dam. The list of differential diagnoses for lameness in rhinoceroses must be expanded by processes affecting other than the extremities per se.

Natural mutation in the regulatory gene (srrG) influences virulence-associated genes and enhances invasiveness in Streptococcus dysgalactiae subsp. equisimilis strains isolated from cases of streptococcal toxic shock syndrome.

BACKGROUND: Streptococcus dysgalactiae subspecies equisimilis (SDSE) has emerged as an important cause of severe invasive infections including streptococcal toxic shock syndrome (STSS). The present study aimed to identify genes involved in differences in invasiveness between STSS and non-invasive SDSE isolates. METHODS: STSS and non-invasive SDSE isolates were analysed to identify csrS/csrR mutations, followed by a comparative analysis of genomic sequences to identify mutations in other genes. Mutant strains were generated to examine changes in gene expression profiles and altered pathogenicity in mice. FINDINGS: Of the 79 STSS-SDSE clinical isolates, 15 (19.0%) harboured csrS/csrR mutations, while none were found in the non-invasive SDSE isolates. We identified a small RNA (sRNA) that comprised three direct repeats along with an inverted repeat and was transcribed in the same direction as the sagA gene. The sRNA was referred to as srrG (streptolysin S regulatory RNA in GGS). srrG mutations were identified in the STSS-SDSE strains and were found to be associated with elevated expression of the streptolysin S (SLS) gene cluster and enhanced pathogenicity in mice. INTERPRETATION: The csrS/csrR and srrG mutations that increased virulence gene expression in STSS-SDSE isolates were identified, and strains carrying these mutations caused increased lethality in mice. A significantly higher frequency of mutations was observed in STSS-SDSE isolates, thereby highlighting their importance in STSS. FUNDING: Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science (JSPS), and the Ministry of Health, Labor, and Welfare of Japan.

Invasive infection due to Streptococcus dysgalactiae subspecies equisimilis causing endocarditis and ventriculitis: A case report.

We aim to raise awareness of the role of Streptococcus dysgalactiae subsp. equisimilis (SDSE) in causing endovascular and central nervous system infections, and to promote recognition of SDSE as a pathogen that may cause serious invasive infections.

In-hospital mortality among patients with invasive non-group A ß-hemolytic Streptococcus treated with clindamycin combination therapy: a nationwide cohort study.

AIM: Combination treatment with clindamycin is recommended in patients with invasive group A Streptococcus infection; however, whether the same treatment is effective in invasive group B Streptococcus and S. dysgalactiae subspecies equisimilis infections remains unknown. We aimed to investigate whether clindamycin added to standard of care therapy would be effective in patients with invasive non-group A ß-hemolytic Streptococcus infections. METHODS: This was a nationwide retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database focusing on the period between 2010 and 2018. We extracted data on patients diagnosed with sepsis due to non-group A ß-hemolytic Streptococcus. One-to-four propensity score-matching was undertaken to compare patients who were treated with clindamycin within 2 days of admission (clindamycin group) and those who did not (control group). The primary outcome was in-hospital mortality. RESULTS: We identified 3754 eligible patients during the study period. The patients were divided into the clindamycin (n = 296) and control groups (n = 3458). After one-to-four propensity score matching, we compared 289 and 1156 patients with and without clindamycin, respectively. In-hospital mortality did not significantly differ between the two groups (9.7% versus 10.3%; risk difference 0.3%; 95% confidence interval, -3.5% to 4.2%). CONCLUSIONS: This nationwide database study showed that combination therapy involving the use of clindamycin was not associated with lower in-hospital mortality in patients with invasive non-group A ß-hemolytic Streptococcus.

High prevalence of pharyngeal bacterial pathogens among healthy adolescents and young adults.

The pharyngeal mucosa can be colonized with bacteria that have potential to cause pharyngotonsillitis. By the use of culturing techniques and PCR, we aimed to assess the prevalence of bacterial pharyngeal pathogens among healthy adolescents and young adults. We performed a cross-sectional study in a community-based cohort of 217 healthy individuals between 16 and 25 years of age. Samples were analyzed for Group A streptococci (GAS), Group C/G streptococci (SDSE), Fusobacterium necrophorum, and Arcanobacterium haemolyticum. Compared to culturing, the PCR method resulted in more frequent detection, albeit in most cases with low levels of DNA, of GAS (20/217 vs. 5/217; p < 0.01) and F. necrophorum (20/217 vs. 8/217; p < 0.01). Culturing and PCR yielded similar rates of SDSE detection (14/217 vs. 12/217; p = 0.73). Arcanobacterium haemolyticum was rarely detected (3/217), and only by PCR. Overall, in 25.3% (55/217) of these healthy adolescents and young adults at least one of these pathogens was detected, a rate that is higher than previously described. Further studies are needed before clinical adoption of PCR-based detection methods for pharyngeal bacterial pathogens, as our findings suggest a high incidence of asymptomatic carriage among adolescents and young adults without throat infections.