Toxic Shock Syndrome: Rare but Deadly.

Invasive group A streptococcal (GAS) disease, although rare, has a high mortality and morbidity rate, making early recognition and treatment crucial. Toxic shock syndrome (TSS) and necrotizing fasciitis are the most feared complications and require comprehensive, multidisciplinary treatment. In addition to appropriate support and resuscitation, patient management should include empirical broad-spectrum antibiotic therapy covering gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and anti-toxin therapy. Early surgical debridement is essential for improving the patient's prognosis, and other treatments, such as immunoglobulin and hyperbaric oxygen therapy (HBOT), also appear to be important. The authors describe the clinical case of a 31-year-old man with no medical history or risk factors, who developed invasive disease from Streptococcus pyogenes with rapid progression to necrotizing fasciitis, TSS, and severe multi-organ dysfunction. His management required intensive care, multiple surgical debridements, admission to the intensive care unit, and targeted as well as supportive therapy. The patient survived, but nearly a year later, he has yet to fully return to a normal life.

A Case of Necrotizing Fasciitis/Myositis and Streptococcal Toxic Shock Syndrome Caused by emm22/ST46 Strain of Streptococcus pyogenes.

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), can cause severe invasive diseases with high fatality rates. We report a case of necrotizing fasciitis and myositis complicated by Streptococcal Toxic Shock-Like Syndrome (STSS) caused by the invasive emm22/ST46 strain of Streptococcus pyogenes in China. A previously healthy 57-year-old Chinese Canadian man presented with right calf pain and ulceration following a hike in the Gobi Desert, which progressed to unconsciousness and severe infection. Despite initial treatment, his condition deteriorated, leading to his transfer to our intensive care unit. Metagenomic Next-Generation Sequencing identified Streptococcus pyogenes, and antimicrobial susceptibility testing revealed resistance to erythromycin, tetracycline, and clindamycin. Despite broad-spectrum antimicrobial therapy, debridement, and supportive measures, the patient's condition necessitated amputation of the right lower limb. He recovered and was discharged from the hospital on Day 43. Whole-genome sequencing of the isolate identified 15 multiple virulence factors. Phylogenetic analysis revealed that the closest relative of the isolate was a strain identified in China. This case underscores the importance of early recognition and treatment of invasive GAS infections to prevent severe outcomes, and we should pay attention to invasive emm22/ST46 GAS infections in China.

Two Cases of Group A Streptococcus-Induced Right Empyema: Rare Occurrences in Adult Medicine.

Group A Streptococcus (GAS) empyema, though rare in adults, poses serious clinical challenges. We present two cases of GAS-induced right empyema in immunocompetent patients. Case 1 involved a 45-year-old female Chinese healthcare worker with persistent pleural effusion despite antibiotic therapy. GAS was isolated from her sputum and bronchoalveolar lavage, necessitating a treatment shift to clindamycin and co-amoxiclav. Case 2 featured a 55-year-old Filipino domestic helper exhibiting right lower chest consolidation and effusion. Thoracocentesis confirmed empyema, prompting intrapleural fibrinolytic administration. Both cases highlight the diagnostic complexity and therapeutic intricacies of adult GAS empyema, underscoring the importance of early recognition and tailored management strategies for optimal patient outcomes.

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.

The intricate pathogenicity of group a Streptococcus: A comprehensive update.

Group A Streptococcus (GAS) is a versatile pathogen that targets human lymphoid, decidual, skin, and soft tissues. Recent advancements have shed light on its airborne transmission, lymphatic spread, and interactions with neuronal systems. GAS promotes severe inflammation through mechanisms involving inflammasomes, IL-1ß, and T-cell hyperactivation. Additionally, it secretes factors that directly induce skin necrosis via Gasdermin activation and sustains survival and replication in human blood through sophisticated immune evasion strategies. These include lysis of erythrocytes, using red cell membranes for camouflage, resisting antimicrobial peptides, evading phagocytosis, escaping from neutrophil extracellular traps (NETs), inactivating chemokines, and cleaving targeted antibodies. GAS also employs molecular mimicry to traverse connective tissues undetected and exploits the host's fibrinolytic system, which contributes to its stealth and potential for causing autoimmune conditions after repeated infections. Secreted toxins disrupt host cell membranes, enhancing intracellular survival and directly activating nociceptor neurons to induce pain. Remarkably, GAS possesses mechanisms for precise genome editing to defend against phages, and its fibrinolytic capabilities have found applications in medicine. Immune responses to GAS are paradoxical: robust responses to its virulence factors correlate with more severe disease, whereas recurrent infections often show diminished immune reactions. This review focuses on the multifaceted virulence of GAS and introduces novel concepts in understanding its pathogenicity.

Case Report: MDFIC gene mutation resulting in central conducting lymphatic anomaly facilitates group A Streptococcus sepsis.

Background: Central conducting lymphatic anomaly (CCLA) is a heterogeneous disorder characterized by structural anomalies in the main collecting lymphatic vasculature. These anomalies result in chronic chylous leaks, causing issues such as congenital hydrothorax and potentially impairing the normal immune response. Recently, mutations in the MyoD family inhibitor domain-containing (MDFIC) gene have been identified as a cause of CCLA. Group A Streptococcus infections are common, and timely identification of patients at risk for severe complications is crucial. Case presentation: Here, we present the case of a 13-year-old female patient with CCLA associated with an MDFIC mutation, who suffered from a severe group A Streptococcus sepsis. Initially, the patient was unresponsive to aggressive fluid resuscitation. Although the course of the sepsis was severe, standardized treatment according to the surviving sepsis campaign proved effective in stabilizing the patient. Discussion: The patient's MDFIC mutation may have contributed to the severe clinical course of the sepsis. It is theorized that this mutation affects the function of the immune system both indirectly, by causing CCLA, and directly, by potentially influencing transcriptional activity in immune cells. More research on the effect of MDFIC mutations on immune responses is required.

Novel Diagnostic Approach for Acute Pharyngitis: Combining Machine Learning With Thermal Imaging.

We evaluated the effect of infrared thermography (IRT) on the clinical assessment of bacterial and viral pharyngitis and its impact on the predictive value of the McIsaac score algorithm for streptococcal pharyngitis in children. We also investigated if IRT could distinguish between bacterial and viral pharyngitis. The study included children aged 2-17 years presenting with sore throat and fever over 38°C from November 1, 2021, to April 30, 2022. Of the 76 assessed children, 16 were excluded due to missing data or technical issues, leaving 60 children (32 males, 28 females) divided into three groups: Group A with streptococcal pharyngitis (N = 30), viral pharyngitis (N = 16), and healthy controls (N = 14). McIsaac score and IRT imaging showed a 90% positive predictive value for streptococcal pharyngitis. While IRT alone could not distinguish between bacterial and viral infections, it significantly increased the predictive value when combined with the McIsaac score.

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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Invasive Group A Streptococcus Hypervirulent M1UK Clone, Canada, 2018-2023.

To determine invasive group A Streptococcus trends in Canada, we characterized emm1 isolates collected during 2018-2023. The percentage of hypervirulent M1UK lineage isolates increased significantly, from 22.1% in 2018 to 60.2% in 2023. Genomic analysis identified geographically and temporally associated clusters and genes associated with virulent bacteriophage acquisition.

Computerized Decision Support Systems Informing Community-Acquired Pneumonia Surveillance, France, 2017-2023.

We show the value of real-time data generated by a computerized decision support system in primary care in strengthening pneumonia surveillance. The system showed a 66% (95% CI 64%-67%) increase in community-acquired pneumonia from 2018 to 2023 for the population of France, 1 month before a national alert was issued.

Epidemiology of Streptococcus pyogenes Disease before, during, and after COVID-19 Pandemic, Germany, 2005-2023.

We analyzed 3,081 invasive and noninvasive Streptococcus pyogenes cases (January 2005-December 2023) at a tertiary care hospital in southwest Germany. Absolute numbers of case-patients increased each year from 2005 until the COVID-19 pandemic. Odds ratios for invasive streptococcal disease were significantly influenced by year, male sex, and older age.

A multicentre observational study of paediatric head and neck abscesses.

INTRODUCTION: In winter of 2022/3 paediatric ENT surgeons across the UK observed that the incidence of severe abscesses in the head and neck and associated complications was higher than seen in previous years. We aimed to collate and evaluate data from across the UK to establish if this was a true rise in cases, and to describe the factors associated. METHODS: A multicentre retrospective data collection was undertaken from 13 units across the UK. Patients admitted between September 2022-February 2023 with a head and neck abscess including sinogenic, otogenic, deep and superficial neck abscesses were included. Demographic, disease specific, management and outcome data were collected. Hospital episode statistic data were also requested and analysed to allow for comparison with previous 10 years of head and neck abscesses. RESULTS: 262 patients with abscesses of the head and neck were admitted during the study period, 100 between September and November and 163 between December and February. Mastoid abscesses were the most common abscess across both groups. The rate of group A streptococcus + culture results rose significantly from 12 % in autumn group to 30 % in winter (p = 0.02). The rate of intracranial complications rose from 10 % to 18 % (p = 0.11) and the rate of venous thrombosis rose over the same timeframe from 3 % to 14 % (p = 0.01). DISCUSSION: This study demonstrated a statistically significant rise in the rate of group A streptococcus associated abscesses when comparing Autumn and Winter 2022/2023. Over the same timeframe a statistically significant rise in the proportion of patients with venous thromboses associated with H&N abscesses was noted. Interestingly, despite perceived national consensus regarding a spike in abscess incidence, the number of abscesses seen in winter 2022/2023 was in keeping with expected rates of paediatric H&N abscesses, based on pre covid year-on-year rise in incidence.

Epidemiology of scarlet fever in Victoria, Australia, 2007-2017.

In the last 10-15 years, there has been a global resurgence of scarlet fever, an infection historically associated with significant morbidity and mortality. It is unknown whether scarlet fever incidence has increased in Australia. We aimed to examine the incidence, predictors and severity of scarlet fever in the state of Victoria, Australia from 2007 to 2017, analyzing scarlet fever emergency department (ED) presentations, hospitalizations and deaths. Of the 1 578 scarlet fever cases during the study period, most occurred in children aged <10 years (1 344, 85%), in males (882, 56%), and during winter and spring months (918, 57%). There were no deaths with scarlet fever, however, 374 cases (24%) were admitted to hospital. The annual incidence of scarlet fever was stable during the study period (mean, 2.5; range, 1.9-3.1 cases per 100 000). Annual incidence was highest in children aged <5 years (19.3 per 100 000), and was 21% higher in males than females, adjusting for age and year (incidence rate ratio, 1.21, 95%CI 1.09-1.34). Whilst scarlet fever ED presentations and hospitalizations were stable in Victoria from 2007 to 2017, the recent identification of a Streptococcus pyogenes variant in Australia associated with epidemic scarlet fever overseas highlights the risk of future outbreaks.

Post-pandemic increase in invasive group A strep infections in New Zealand.

BACKGROUND: Since October 2022, multiple high-income countries have reported an increase in invasive group A streptococcal (iGAS) infections. This study describes trends in iGAS infections in Aotearoa New Zealand (NZ) between 2017 and 2023, and examines associations of iGAS incidence, COVID-19 eras, and acute respiratory infections (ARI). METHODS: Analyses include national-level surveillance data on iGAS and ARI. Multivariable Poisson regression was used to examine relationships between COVID-19 era and iGAS incidence, and Pearson pairwise correlations were calculated to examine trends between ARI and iGAS. FINDINGS: A sharp increase in iGAS was observed in 2023, with notable increases among children aged under ten years. Indigenous Maori and Pacific peoples were disproportionately affected. emm1 and emm12 were commonly reported in 2022-2023. Compared to pre-pandemic, iGAS decreased significantly during the COVID-19 restrictions era and increased once COVID-19 restrictions were relaxed, after adjusting for ethnicity, sex, and age. ARI was moderately correlated with iGAS (r = 0∙55) in 2022-2023. INTERPRETATION: Though delayed, NZ's recent iGAS trends mirror those seen in the 2022/2023 multi-country iGAS surge. These findings expand existing research, suggesting a link between the easing of COVID-19 measures, increased ARI circulation, and the rise in iGAS. Continued and improved iGAS surveillance, is needed to better understand iGAS epidemiology and support public health response. iGAS in NZ will become notifiable in late 2024, which should help improve iGAS monitoring and support public health response. FUNDING: This research received no specific funding, though iGAS surveillance and typing in NZ is funded by the Ministry of Health, which was not involved in the analysis, interpretation, design, or any aspect of this study. No authors were paid to write this manuscript.

Ongoing Excess Hospitalizations for Severe Pediatric Group A Streptococcal Disease in 2023-2024-A Single-Center Report.

A Europe-wide outbreak of invasive pediatric group A streptococcal infections (iGAS) began in fall 2022. Here, we report the evolution of GAS hospitalizations in children and adolescents during the second outbreak year in 2023-2024 at a tertiary center in Switzerland. Using prospective monitoring of all in-patient GAS cases below 16 years of age, including those with iGAS, we compared case frequencies and clinical characteristics in three time periods (2013-2020; 2022-2023; 2023-2024). Annual GAS hospitalizations increased from a median of 25 cases (range 11-28) in 2013-2020 to 89 and 63 cases, respectively, in 2022-2023 and 2023-2024. iGAS cases evolved similarly (2013-2020, 4 cases (3-8); 2022-2023, 32 cases; 2023-2024, 21 cases). The decline in cases from 2022-2023 to 2023-2024 included all types of GAS organ involvement, except suppurative infections in the head area, which remained largely unchanged (48 vs. 45 cases). Pleural empyema declined from 13 to 7 cases, possibly explained by a poor overlap of the GAS and influenza curves, respectively, in 2023-2024 compared to 2022-2023. These data document the prolongation of the GAS outbreak into its second winter season in 2023-2024.

A severe case of reactive infectious mucocutaneous eruption associated with two possible triggers: Coronavirus and group A streptococcus.

Reactive infectious mucocutaneous eruption (RIME) is a newly defined condition characterized by mucocutaneous blistering secondary to upper respiratory infections and encompasses Mycoplasma pneumoniae-induced rash and mucositis, broadening the disease spectrum to include various infectious etiologies. We present a severe RIME case involving a 5-year-old female with concurrent coronavirus NL63 and group A streptococcus infections. Diagnosis complexity stemmed from overlapping clinical features with other severe mucocutaneous eruptions such as Stevens-Johnson syndrome/toxic epidermal necrolysis/drug-induced necrolysis. This case underscores the need for comprehensive infectious workup and emphasizes the clinical diagnostic spectrum of drug-induced and infection-induced desquamative skin and mucosal disease.

Streptococcus pyogenes flexor tenosynovitis.

We describe a case of Group A streptococcal infection originally presenting as flexor tenosynovitis. Group A Streptococcus outbreaks have been recently described in developed countries, which constitutes an epidemiological shift that hand surgeons should be aware of.

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

BACKGROUND: Despite 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. METHODS: In 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. RESULTS: Among 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. CONCLUSIONS: We 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.

Treatment outcomes and their predictors in children hospitalized with varicella complicated by bacterial superinfections after pandemic of COVID-19 - a retrospective multicenter analysis of real-life data in Poland.

PURPOSE: The aim of this study was to analyze treatment outcomes and their predictors in children hospitalized due to varicella complicated by bacterial superinfections after pandemic of COVID-19. METHODS: This retrospective study analyzed data collected in a multicenter, nationwide, observational database dedicated for children aged 0-17 years hospitalized due to bacterial complications of varicella in 9 Polish tertiary healthcare inpatient centers. The primary endpoint of this study was the treatment outcome established after the end of hospital management assessed at a 4-point scale. The secondary endpoint was defined as the necessity of surgical intervention. RESULTS: There were 458 patients with a median age of 4 (IQR 2-6) years. After the completed treatment, 319 (69%) participants were found fully recovered; 132 (29%) had transient complications; 2 (0.5%) had persistent complications; and 1 child (0.5%) died. Multivariate analysis revealed that implementation of ibuprofen in pre-treatment management of a child with varicella was associated with a 4.07-fold (2.50-6.60) increase in risk of complications after the treatment and it was associated with 2.87 times (1.39-5.89) higher risk of surgical intervention necessity. For other pre-hospital interventions (implementation of acyclovir, antibiotics or antihistaminics) no significant impact was observed. GAS infection increased the necessity of surgical intervention by 7.51 (3.64-15.49) times. CONCLUSIONS: One-third of patients treated for bacterial complications of varicella have post-treatment complications, most of them transient. GAS infection increases the need for surgical intervention. The use of ibuprofen in the treatment of varicella significantly increases the risk of complications and the need for surgical intervention.