Group A Streptococcal Infections Research Articles

Unveiling the Group A Streptococcus Vaccine-Based L-Rhamnose from Backbone of Group A Carbohydrate: Current Insight Against Acute Rheumatic Fever to Reduce the Global Burden of Rheumatic Heart Disease

Group A Streptococcus (GAS) is a widely distributed bacterium that is Gram-positive and serves as the primary cause of acute rheumatic fever (ARF) episodes. Rheumatic heart disease (RHD) is a sequela resulting from repeated ARF attacks which are also caused by repeated GAS infections. ARF/RHD morbidity and mortality rates are incredibly high in low- and middle-income countries. This is closely related to poor levels of sanitation which causes the enhanced incidence of GAS infections. Management of carditis in RHD cases is quite challenging, particularly in developing countries, considering that medical treatment is only palliative, while definitive treatment often requires more invasive procedures with high costs. Preventive action through vaccination against GAS infection is one of the most effective steps as a solution in reducing RHD morbidity and mortality due to curative treatments are expensive. Various developments of M-protein-based GAS vaccines have been carried out over the last few decades and have recently begun to enter the clinical stage. Nevertheless, this vaccination generates cross-reactive antibodies that might trigger ARF assaults as a result of the resemblance between the M-protein structure and proteins found in many human tissues. Consequently, the development of a vaccine utilizing L-Rhamnose derived from the poly-rhamnose backbone of Group A Carbohydrate (GAC) commenced. The L-Rhamnose-based vaccine was chosen due to the absence of the Rhamnose biosynthesis pathway in mammalian cells including humans thus this molecule is not found in any body tissue. Recent pre-clinical studies reveal that L-Rhamnose-based vaccines provide a protective effect by increasing IgG antibody titers without causing cross-reactive antibodies in test animal tissue. These findings demonstrate that the L-Rhamnose-based vaccine possesses strong immunogenicity, which effectively protects against GAS infection while maintaining a significantly higher degree of safety.

Adjunctive linezolid versus clindamycin for toxin inhibition in β-lactam-treated patients with invasive group A streptococcal infections in 195 US hospitals from 2016 to 2021: a retrospective cohort study with target trial emulation.

Adjunctive clindamycin use is associated with survival in invasive group A streptococcus (GAS) infections but increasing clindamycin resistance in GAS has called into question its durability for this indication. Linezolid also inhibits GAS toxin and virulence factor production, but clinical efficacy data remain sparse. We retrospectively emulated a target multicentre, non-blinded, non-inferiority trial to assess the efficacy of adjunctive linezolid compared with clindamycin in adult inpatients with invasive GAS infection treated with a β-lactam using the PINC AI database between 2016 and 2021. Patients were eligible if they had a monomicrobial GAS culture and received adjunctive therapy within 3 days of culture either concurrently or after β-lactam initiation and completed at least 3 days of β-lactam therapy. The primary outcome was adjusted risk ratio (aRR) of in-hospital mortality assessed by overlap-weighting using propensity scores. Secondary outcomes were length of stay among survivors and Clostridium difficile infection. Of 1095 β-lactam-treated patients with GAS, 829 (76%) received clindamycin and 266 (24%) received linezolid. In the overlap weighted cohort, the receipt of linezolid was not associated with a statistically significant different aRR of in-hospital mortality compared with clindamycin (linezolid: 9·8% [26/266] vs clindamycin: 7·0% [58/829]; aRR: 0·92 [95% CI 0·42 to 1·43]; p=0·76). The risk difference was -0·005 (95% CI -0·05 to 0·04; p=0·81) and fell within the non-inferiority margin of 0·05. The primary analysis results were consistent across important subgroups and sensitivity analyses. Among survivors, median length of stay (adjusted ratio 0·96 [95% CI 0·16 to 0·08]; p=0·47) and C difficile infection risk (aRR 1·76 [95% CI 0·37 to 1·75]; p=0·29) were not statistically significantly different between the two groups. In this emulated trial of adult patients with invasive GAS infections treated with β-lactam, linezolid appeared non-inferior to clindamycin suggesting linezolid as an alternative for adjunctive antitoxin therapy. The Intramural Research Program of the US National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Disease.

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

Clusters of invasive group Astreptococcal (iGAS) infection, linked to genomically closely related group Astreptococcal (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. 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. We included all residents in ABCs sites with iGAS infections meeting the case definition and excluded non-conforming GAS infections and cases with whole-genome assemblies of the isolate containing fewer than 1·5million total bases or more than 150contigs. For iGAS cases we collected basic demographics, underlying conditions, and risk factors for infection from medical records, and for isolates we included emm types, antimicrobial resistance, and presence of virulence-related genes. Two iGAS cases were defined as genomically clustered if their isolates differed by three or less single-nucleotide variants. An iGAS case not clustered with any previous cases at the time of detection, with a minimum trace-back time of 1year, was defined as being at risk of cluster formation. We monitored each iGAS case at risk for a minimum of 1year to identify any cluster formation event, defined as the detection of a subsequent iGAS case clustered with the case at risk. We used the Kaplan-Meier method to estimate the cumulative incidence of cluster formation events over time. We used Cox regression to assess associations between features of cases at risk upon detection and subsequent cluster formation. We developed a random survival forest machine-learning model based on a derivation cohort (random selection of 50% of cases at risk) to predict cluster formation risk. This model was validated using a validation cohort consisting of the remaining 50%of cases at risk. We identified 2764iGAS cases at risk from 2016to 2018, of which 656 (24%) formed genomic clusters by the end of 2019. Overall, the cumulative incidence of cluster formation was 0·057 (95% CI 0·048-0·066) at 30days after detection, 0·12 (0·11-0·13) at 90days after detection, and 0·16 (0·15-0·18) at 180days after detection. Ahigher risk of cluster formation was associated with emm type (adjusted hazard ratio as compared with emm89 was 2·37 [95% CI 1·71-3·30] for emm1, 2·72 [1·82-4·06] for emm3, 2·28 [1·49-3·51] for emm6, 1·47 [1·05-2·06] for emm12, and 2·21 [1·38-3·56] for emm92), homelessness (1·42 [1·01-1·99]), injection drug use (2·08 [1·59-2·72]), residence in a long-term care facility (1·78[1·29-2·45]), and the autumn-winter season (1·34 [1·14-1·57]) in multivariable Cox regression analysis. The machine-learning model stratified the validation cohort (n=1382) into groups at low (n=370), moderate (n=738), and high (n=274) risk. The 90-day risk of cluster formation was 0·03 (95% CI 0·01-0·05) for the group at low risk, 0·10(0·08-0·13) for the group at moderate risk, and 0·21 (0·17-0·25) for the group at high risk. These results were consistent with the cross-validation outcomes in the derivation cohort. Using population-based surveillance data, we found that pathogen, host, and environment factors of iGAS cases were associated with increased likelihood of subsequent genomic cluster formation. Groups at high risk were consistently identified by a predictive model which could inform prevention strategies, although future work to refine the model, incorporating other potential risk factors such as host contact patterns and immunity to GAS, is needed to improve its predictive performance. Centers for Disease Control and Prevention.

Acute disseminated encephalomyelitis (ADEM) in a patient with post streptococcal glomerulonephritis (PSGN): A case report.

Concurrent recurrence of acute disseminated encephalomyelitis (ADEM) and poststreptococcal glomerulonephritis (PSGN) in a thalassemia intermedia patient is rare and underscores the complexity of autoimmune disorders. This case emphasizes the importance of considering ADEM in the differential diagnosis of children presenting with PSGN accompanied by neurological symptoms. Post-streptococcal glomerulonephritis (PSGN) is a common group A streptococcal (GAS) infection sequela. The pathophysiology of PSGN involves immune complex deposition, with type 3 hypersensitivity reaction triggered by GAS. Certain neurological conditions may also arise following a GAS infection, possibly due to molecular mimicry in the brain, a pathophysiology similar to rheumatic fever, another common sequel of GAS infection. We present the case of a child with β-thalassemia intermedia who exhibited the classic triad (edema, hypertension, hematuria) of PSGN along with neurological manifestations, including a low glasgow coma scale (GCS) score and seizures. Magnetic resonance imaging (MRI) of the brain indicated changes consistent with acute disseminated encephalomyelitis (ADEM). Initially treated with methylprednisolone, the patient eventually received intravenous immunoglobulin (IVIG) due to lack of response. The patient had a good outcome, with complete resolution of all symptoms and no residual neurological deficits. This case underscores the importance of considering ADEM in the differential diagnosis for patients presenting with neurological signs and symptoms following a recent throat infection with GAS. Furthermore, given the increased risk of infection in thalassemia, patients with thalassemia who have a throat infection and neurological symptoms should be evaluated for the possible presence of ADEM.

Impact of the COVID-19 Pandemic on Group A Streptococcal Necrotizing Soft Tissue Infections: A Retrospective Cohort Study.

Necrotizing soft tissue infections (NSTIs) are often caused by group A Streptococcus (GAS). As the number of invasive GAS infections decreased during the coronavirus disease 2019 (COVID-19) pandemic restrictions, this study aimed to compare the occurrence of GAS-NSTIs before, during, and after the COVID-19 pandemic restrictions. This retrospective cohort study included adult patients with NSTIs admitted to the intensive care unit (ICU) of the University Hospital Zurich, Switzerland, from July 2008 to December 2023. NSTI cases were categorized as pre-, during, and postrestrictions. The primary outcome was the proportion of GAS in NSTI, and the exploratory secondary outcome was in-hospital death. A data analysis was conducted using Firth logistic regression adjusted for age, sex, diabetes, and initially affected body region. Overall, 74 NSTI cases were identified, with 49 occurring before, 8 during, and 17 after the pandemic restrictions. GAS was isolated in 27 (36%) cases, with 17 (35%) pre- and 10 (59%) postrestrictions, but none during the restrictions. NSTIs caused by other bacteria persisted during the restrictions. The odds of GAS were significantly lower during the restrictions (adjusted odds ratio, 0.02; 95% CI, 0.001-0.81) compared with after, while no significant differences were found between the pre- and postrestriction periods. The significant decrease of GAS-NSTIs during the COVID-19 pandemic restrictions suggests that isolation measures may have prevented the transmission of GAS, resulting in a decline of GAS-NSTIs while NSTIs caused by bacteria transmitted by alternative routes persisted.

Group A Streptococcus infections in children and adolescents in the post-COVID-19 era: a regional Italian survey

BackgroundDespite the worldwide increasing incidence of Group A Streptococcus (GAS) infections reported since December 2022, data on noninvasive GAS (nGAS) infections in the post COVID-19 era are limited. By a self-reported survey performed in an outpatient setting, we investigated the number and clinical features of GAS infections, the diagnostic work-up and the type of treatment utilized. In addition, the rate of influenza vaccination was evaluated.MethodsIn June 2023 family pediatricians involved in the study sent the survey to parents of patients aged 0–16 years. The survey included questions on GAS infections that occurred from January 1 to May 31, 2023.ResultsAmong 3580 children, 20.3% had a GAS infection (0,8% < 1 year, 16,4% 1–3 years, 42,3% 3–6 years, 26,5% 6–9 years, 11,4%, 9–12 years, and 2,6% 12–16 years). Symptoms reported were sore throat (76.9%), fever (75.2%), tonsillar exudate (25.2%), lymphadenopathy (21.8%), and scarlet fever (14.7%). A single patient was hospitalized due to GAS meningitis.Twenty four percent of children had more than one GAS infection. In this group, frequencies of symptoms reported in the first and in the following infection were similar, except for fever and scarlet fever which were less frequent during relapses. GAS was identified by rapid antigen detection test in 81.0% of children. Eighty-nine per cent of children were treated with antibiotics, mostly amoxicillin/clavulanate (40.4%) and amoxicillin (39.4%). Thirty four percent of children received influenza vaccine. No difference was observed among immunized and not immunized regarding the number and characteristics of GAS infection. ConclusionsWe reported a certain prevalence of nGAS infections in children, mainly those aged 3–6 years age, who were mostly characterized by a low score of symptoms, and in most of the cases diagnosed and treated using a microbiological test as confirmatory tool.In this new clinical setting, a national study would be useful to reach more significant data for the definition of a correct diagnosis and clinical management of nGAS infections in children. Moreover, it is important to improve flu vaccination campaign and coverage to protect children from coinfections that could worsen the disease and misdiagnose the etiology of pharyngitis.

Chains of misery: surging invasive group A streptococcal disease.

We describe the epidemiology of the recent global surge in invasive group A streptococcal (GAS) disease and consider its proximate and distal causes. We highlight important knowledge gaps regarding clinical management and discuss potential strategies for prevention. Rates of invasive GAS (iGAS) disease were increasing globally prior to the COVID-19 pandemic. Since mid-2022, following the worst years of the pandemic in 2020 and 2021, many countries with systems to monitor GAS syndromes have reported surges in cases of iGAS concurrent with increased scarlet fever, pharyngitis, and viral co-infections. The emergence of the hypervirulent M1UK strain as a cause of iGAS, particularly in high income countries, is concerning. New data are emerging on the transmission dynamics of GAS. GAS remains universally susceptible to penicillin but there are increasing reports of macrolide and lincosamide resistance, particularly in invasive isolates, with uncertain clinical consequences. Intravenous immunoglobulin is used widely for streptococcal toxic shock syndrome and necrotizing soft tissue infections, although there is limited clinical evidence, and none from a completed randomized controlled trial. Intensive and expensive efforts at population-level control of GAS infections and postinfectious autoimmune complications have been only partially successful. The great hope for control of GAS diseases remains vaccine development. However, all modern vaccine candidates remain in the early development stage. In many countries, iGAS rates surged from mid-2022 in the aftermath of pandemic control measures and physical distancing. The emergence of a dominant hypervirulent strain is an important but incomplete explanation for this phenomenon. Clinical management of iGAS remains highly empirical and new data has not emerged. A vaccine remains the most likely means of achieving a sustainable reduction in the burden of iGAS.

Efficient and rapid one-step method to generate gene deletions in Streptococcus pyogenes.

Group A Streptococcus (GAS) is a major human pathogen, causing diseases ranging from mild and superficial infections of the skin and pharyngeal epithelium to severe systemic and invasive diseases. Since June 2022, several European countries, the US, and Australia are facing an upsurge of invasive life-threatening GAS infections. Finding a good vaccine antigen and understanding the role of virulence factors in GAS infections have been hampered, in part, by technical difficulties to transform the many different GAS strains and generate knockout mutants. Moreover, these tools must be adapted to a large range of different strains, since GAS are divided into more than 260 emm-types (M-type). We have set up a method allowing the generation of non-polar mutants of GAS in 3 days and in diverse backgrounds, which contrasts with previously published protocols.

Manganese uptake by MtsABC contributes to the pathogenesis of human pathogen group A streptococcus by resisting host nutritional immune defenses.

The interplay between host nutritional immune mechanisms and bacterial nutrient uptake systems has a major impact on the disease outcome. The host immune factor calprotectin (CP) limits the availability of essential transition metals, such as manganese (Mn) and zinc (Zn), to control the growth of invading pathogens. We previously demonstrated that the competition between CP and the human pathogen group A streptococcus (GAS) for Zn impacts GAS pathogenesis. However, the contribution of Mn sequestration by CP in GAS infection control and the role of GAS Mn acquisition systems in overcoming host-imposed Mn limitation remain unknown. Using a combination of in vitro and in vivo studies, we show that GAS-encoded mtsABC is a Mn uptake system that aids bacterial evasion of CP-imposed Mn scarcity and promotes GAS virulence. Mn deficiency caused by either the inactivation of mtsC or CP also impaired the protective function of GAS-encoded Mn-dependent superoxide dismutase. Our ex vivo studies using human saliva show that saliva is a Mn-scant body fluid, and Mn acquisition by MtsABC is critical for GAS survival in human saliva. Finally, animal infection studies using wild-type (WT) and CP-/- mice showed that MtsABC is critical for GAS virulence in WT mice but dispensable in mice lacking CP, indicating the direct interplay between MtsABC and CP in vivo. Together, our studies elucidate the role of the Mn import system in GAS evasion of host-imposed metal sequestration and underscore the translational potential of MtsABC as a therapeutic or prophylactic target.

Emergent emm4 group A Streptococcus evidences a survival strategy during interaction with immune effector cells.

The major gram-positive pathogen group A Streptococcus (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics have been ascribed to the emergence of clones producing increased amounts of key virulence factors such as streptolysin O (SLO). Herein, we sought to identify mechanisms underlying our recently identified temporal clonal emergence among emm4 GAS, given that emergent strains did not produce augmented levels of virulence factors relative to historic isolates. By creating and analyzing isoallelic strains, we determined that a conserved mutation in a previously undescribed gene encoding a putative carbonic anhydrase was responsible for the defective in vitro growth observed in the emergent strains. We also identified that the emergent strains survived better inside macrophages and killed macrophages at lower rates than the historic strains. Via the creation of isogenic mutant strains, we linked the emergent strain "survival" phenotype to the downregulation of the SLO encoding gene and upregulation of the msrAB operon which encodes proteins involved in defense against extracellular oxidative stress. Our findings are in accord with recent surveillance studies which found a high ratio of mucosal (i.e., pharyngeal) relative to invasive infections among emm4 GAS. Since ever-increasing virulence is unlikely to be evolutionarily advantageous for a microbial pathogen, our data further understanding of the well-described oscillating patterns of virulent GAS infections by demonstrating mechanisms by which emergent strains adapt a "survival" strategy to outcompete previously circulating isolates.

Rising clindamycin resistance in group A Streptococcus in an Irish healthcare institution.

Group A streptococcus (GAS) can cause serious invasive disease in humans with a high mortality rate. An increase in GAS infections was reported in Ireland in 2022, and this increase has been sustained in 2023 and is paralleled by similar trends in Europe. Rising antimicrobial resistance is a global problem and presents significant challenges to clinicians treating GAS infection. There was a reported increase in clindamycin resistance in GAS isolates in Ireland in 2022. We examined antimicrobial susceptibility patterns of GAS isolates in our institution in 2022. Although all GAS isolates included in our study were susceptible to penicillin, we noted a high clindamycin resistance rate of 28 % in our invasive GAS isolates. We also noted high tetracycline and erythromycin resistance, 43 and 30 %, respectively. Our results could have implications for empiric antimicrobial prescribing guidelines for skin and soft tissue infections, which often include clindamycin as it inhibits the production of many virulence factors associated with GAS. In addition, macrolides are often the first line recommended antibiotic for patients with anaphylaxis to penicillin. This study emphasises the importance of continuous surveillance and antimicrobial susceptibility testing of invasive and non-invasive isolates in order to monitor trends in increasing antimicrobial resistance.

Infection route associated with invasive group A streptococcal toxic shock syndrome in maternal deaths: Nationwide analysis of maternal mortalities in Japan

ObjectivesTo clarify the infection route in maternal death due to invasive group A streptococcal (GAS) infection and toxic shock syndrome (TSS). MethodsA retrospective study was conducted on maternal deaths due to GAS-TSS in Japan between January 2010 and March 2024. The final causal diagnosis of maternal death and the infection routes of GAS were analysed using medical records, laboratory data and autopsy findings. ResultsAmong the 616 maternal deaths during the study period, 48 (8%) involved infectious diseases. The most common infection was invasive GAS (56%, n = 27), 21 (78%) and six cases occurred during the antepartum and puerperium periods, respectively. In the GAS-TSS group, 71% (15/21) infections were originated the upper respiratory tract. However, in the puerperium cases, 67% (4/6) were infected from the genital tract. In addition, no maternal deaths due to GAS-TSS were reported during the COVID-19 pandemic period in Japan from 2020 to 2023. ConclusionMost antepartum GAS infections were from the upper respiratory tract. They may be reduced by preventive measures, including frequent disinfection, wearing masks and isolation from persons at high risk of carrying GAS, such as symptomatic children. On the other hand, GAS-TSS during puerperium infection via the genital tract.

Molecular Epidemiology of Group A Streptococcus Isolated from Children in Beijing during 2011 to 2019

Abstract Objective This study aimed to examine the characteristics of Group A Streptococcus (GAS) infection and identify the emm genotypes and the superantigen gene of GAS strains isolated from children from 2011 to 2019 in Tongzhou District, Beijing. Methods Pharyngeal swab samples from children with scarlet fever or pharyngeal infection were collected and tested for GAS. In GAS isolates, emm genotypes and superantigen genes were identified. Logistic regression models were used to explore the correlations between demographic characteristics, clinical manifestations, and GAS infection. Results In total, 172/1,214 (14.2%) GAS were isolated. The GAS infection rate in children with scarlet fever was 47.5%, higher than 8.5% in children with pharyngeal infection (p &lt; 0.001). The risk of GAS infection was associated with oral mucosal congestion in children with scarlet fever, and older age, tonsillitis, and rash in children with pharyngeal infection. Seven emm genotypes were detected in 164 GAS isolated strains, of which emm12 and emm1 accounted for 47.0 and 46.3%, respectively. Among 112 GAS isolates, the top 5 detection rates of superantigen genes were speF 100.0%, speG 100.0%, speB 98.2%, speC 94.6%, and smeZ 82.1%. Higher proportions of speA, speJ, and speK were detected in emm1 isolates, while speH and speI were more common in emm12 isolates (p &lt; 0.001). Conclusion The changing predominant type expanded the knowledge of the circulating emm types, which should be considered in future vaccine development.

Group A Streptococcus induces lysosomal dysfunction in THP-1 macrophages.

The human-specific bacterial pathogen group A Streptococcus (GAS) is a significant cause of morbidity and mortality. Macrophages are important to control GAS infection, but previous data indicate that GAS can persist in macrophages. In this study, we detail the molecular mechanisms by which GAS survives in THP-1 macrophages. Our fluorescence microscopy studies demonstrate that GAS is readily phagocytosed by macrophages, but persists within phagolysosomes. These phagolysosomes are not acidified, which is in agreement with our findings that GAS cannot survive in low pH environments. We find that the secreted pore-forming toxin Streptolysin O (SLO) perforates the phagolysosomal membrane, allowing leakage of not only protons but also large proteins including the lysosomal protease cathepsin B. Additionally, GAS recruits CD63/LAMP-3, which may contribute to lysosomal permeabilization, especially in the absence of SLO. Thus, although GAS does not inhibit fusion of the lysosome with the phagosome, it has multiple mechanisms to prevent proper phagolysosome function, allowing for persistence of the bacteria within the macrophage. This has important implications for not only the initial response but also the overall functionality of the macrophages, which may lead to the resulting pathologies in GAS infection. Our data suggest that therapies aimed at improving macrophage function may positively impact patient outcomes in GAS infection.

Immune Responses in Children Infected with Streptoccocus A during the Spring 2023 Epidemic in Bulgaria

Streptococcus pyogenes, Group A Streptococcus (GAS), is the most common cause of bacterial tonsillitis, scarlet fever, impetigo, etc. in children and adults. Innate and adaptive host immune responses are fundamental for human defence against GAS, but are also important to the clinical manifestations of the infection. Our aim was to study the humoral and cellular immune responses in children infected with GAS and diagnosed with tonsillitis in the Clinic of Pediatrics in University Hospital “Lozenets”. The study included 22 infected children and 20 healthy controls. The following immune parameters were investigated: i) Humoral immune response – total serum IgG, IgM, IgA; C3, C4 – complement components, as well as the serum cytokines IFNγ, IL-6, IL-1β, TNFα, IL-17A, IL-10. ii) Cellular immune subsets were tested by immunophenotyping of total T cells, B cells, NK cells, T helper and T cytotoxic subsets. In this cross-sectional study we found a significant increase in the complement components C3 and C4, increased production of serum IFNγ, IL-6 and IL-10 and decreased levels of IL-17A in infected children with tonsillitis, compared to healthy controls. The cellular immune parameters in infected children showed lymphopenia, reduced total T lymphocytes and T-helper subpopulation, compared to healthy controls. We assumed that these imbalanced immune responses, found in infected children, are connected with GAS infection and deserved more detailed investigation.

Antibiotic susceptibility of Streptococcus species that cause pharyngitis in children

Background: Group A Streptococcus (GAS) significantly impacts global health, especially among children aged 5–14 years, causing approximately 288 million episodes of sore throat annually and resulting in around 100,000 disability-adjusted life years (DALYs) each year. GAS infections are particularly prevalent in developing countries. Objective: To assess the patterns of antibiotic resistance of Streptococcus spp. that cause pharyngitis in children. Patients and Methods: It was collected 100 pediatric patients. It was taken throat swabs for Streptococcus species culture and antibiotic sensitivity test. In addition, it was recorded the data of patient’s age and gender. Results: It was shown in this study that an average age of 4.4 ± 3.7 years for pharyngitis in children. In this study was diagnosed that Streptococcus agalactiae (24%) and Streptococcus pyogenes (18%) as the common causes Streptococcus species causes pharyngitis in children. It was noted that the differences in bacterial species according to the patient’s ages. Antibiotic sensitivity testing determined that there are high sensitivity of S. pneumoniae and S. parasanguinis to multiple antibiotics. In addition, it was showed resistance of S. pyogenes to Metronidazole and Azithromycin. Conclusion: In this study, it was found that the risk age for pharyngitis in children is four years old. Streptococcus agalactiae and Streptococcus pyogenes are the common bacterial causes for this infection. In addition, it was shown that S. pneumoniae appeared a high sensitivity to Ceftriaxone, Ciprofloxacin, and Meropenem, and S. parasanguinis was sensitive to Azithromycin, Cefixime, and Cefotaxime, and S. pyogenes showed a high sensitivity to Meropenem and Imipenem. Keywords: Pharyngitis, Streptococcus pyogenes, Children infection, antibiotic resistance.

Antibiotic susceptibility of Streptococcus species that cause pharyngitis in children

Background: Group A Streptococcus (GAS) significantly impacts global health, especially among children aged 5–14 years, causing approximately 288 million episodes of sore throat annually and resulting in around 100,000 disability-adjusted life years (DALYs) each year. GAS infections are particularly prevalent in developing countries. Objective: To assess the patterns of antibiotic resistance of Streptococcus spp. that cause pharyngitis in children. Patients and Methods: It was collected 100 pediatric patients. It was taken throat swabs for Streptococcus species culture and antibiotic sensitivity test. In addition, it was recorded the data of patient’s age and gender. Results: It was shown in this study that an average age of 4.4 ± 3.7 years for pharyngitis in children. In this study was diagnosed that Streptococcus agalactiae (24%) and Streptococcus pyogenes (18%) as the common causes Streptococcus species causes pharyngitis in children. It was noted that the differences in bacterial species according to the patient’s ages. Antibiotic sensitivity testing determined that there are high sensitivity of S. pneumoniae and S. parasanguinis to multiple antibiotics. In addition, it was showed resistance of S. pyogenes to Metronidazole and Azithromycin. Conclusion: In this study, it was found that the risk age for pharyngitis in children is four years old. Streptococcus agalactiae and Streptococcus pyogenes are the common bacterial causes for this infection. In addition, it was shown that S. pneumoniae appeared a high sensitivity to Ceftriaxone, Ciprofloxacin, and Meropenem, and S. parasanguinis was sensitive to Azithromycin, Cefixime, and Cefotaxime, and S. pyogenes showed a high sensitivity to Meropenem and Imipenem.

Group A Streptococcal Infections in Pediatric Age: Updates about a Re-Emerging Pathogen.

Group A Streptococcus (GAS) presents a significant global health burden due to its diverse clinical manifestations ranging from mild infections to life-threatening invasive diseases. While historically stable, the incidence of GAS infections declined during the COVID-19 pandemic but resurged following the relaxation of preventive measures. Despite general responsiveness to β-lactam antibiotics, there remains an urgent need for a GAS vaccine due to its substantial global disease burden, particularly in low-resource settings. Vaccine development faces numerous challenges, including the extensive strain diversity, the lack of suitable animal models for testing, potential autoimmune complications, and the need for global distribution, while addressing socioeconomic disparities in vaccine access. Several vaccine candidates are in various stages of development, offering hope for effective prevention strategies in the future.

Recombinational exchange of M-fibril and T-pilus genes generates extensive cell surface diversity in the global group A Streptococcus 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 emm 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. The major pilin adhesin and backbone sequence clusters yield 98 unique combinations, defined as "pilin types." Numerous horizontal transfer events that involve pilin or emm genes generate extensive antigenic and functional diversity on the bacterial cell surface and lead to the emergence of new strains. Inferred pilin genotypes applied to a meta-analysis of global population-based collections of pharyngitis and impetigo isolates reveal highly significant associations between pilin genotypes and GAS infection at distinct ecological niches, consistent with a role for pilin gene products in adaptive evolution. Integration of emm and pilin typing into open-access online tools (pubmlst.org) ensures broad utility for end-users wanting to determine the architecture of M-fibril and T-pilus genes from genome assemblies.IMPORTANCEPrecision in defining the variant forms of infectious agents is critical to understanding their population biology and the epidemiology of associated diseases. Group A Streptococcus (GAS) is a global pathogen that causes a wide range of diseases and displays a highly diverse cell surface due to the antigenic heterogeneity of M-fibril and T-pilus proteins which also act as virulence factors of varied functions. emm genotyping is well-established and highly utilized, but there is no counterpart for pilin genes. A global GAS collection provides the basis for a comprehensive pilin typing scheme, and online tools for determining emm and pilin genotypes are developed. Application of these tools reveals the expansion of structural-functional diversity among GAS via horizontal gene transfer, as evidenced by unique combinations of surface protein genes. Pilin and emm genotype correlations with superficial throat vs skin infection provide new insights on the molecular determinants underlying key ecological and epidemiological trends.

Epidemiological changes of acute respiratory infections in children: A single-center experience after COVID-19 lockdown.

Since the start of the COVID-19 pandemic, the epidemiology of acute respiratory infections (ARIs) has continually changed, making it difficult to predict. Our study aimed to evaluate epidemiological changes and clinical outcomes of ARIs in pediatric patients in the post-lockdown period. A single-center retrospective cross-sectional study was performed in one of the largest pediatric emergency departments in Lithuania during two cold seasons-from October 1, 2021, to April 30, 2022 (Season I) and in the same period in 2022-2023 (Season II). Patients under 18 years of age who had been tested for COVID-19 were enrolled in the study. Additional data about other respiratory pathogens in the study group (specifically influenza A/B, respiratory syncytial virus (RSV) and group A Streptococcus (GAS)), were included. During both seasons of our study, 19,366 children were screened for COVID-19. Positive tests for COVID-19 decreased from 14.5% in Season I to 5.9% in Season II, while at the same time, the rates of other infections increased significantly: influenza from 17.5% to 27.1%, RSV from 8.8% to 27.6%, and GAS from 8.4% to 44%, respectively. In Season II, COVID-19 infection presented in fewer admissions to pediatric intensive care (0.8% vs. 3.7%, p<0.01) and there were no deaths, while influenza presented in a higher proportion of hospitalizations (10.5% vs. 6.1%, p<0.01) and there was one death. The proportion of RSV hospitalizations also increased in Season II (34.6% vs. 44.0%, p<0.01). The early post-lockdown period saw a decline of COVID-19 and re-emergence of influenza, RSV and GAS infections in children. In Season II, COVID-19 cases became milder contrary to influenza. RSV infection contributed significantly to hospitalizations for respiratory infections in children in both seasons, particularly in Season II. Coinfections were not associated with a more severe course of the disease.