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The Pediatric Infectious Disease Journal Jun 2024In winter 2022/2023, a resurgence of invasive group A streptococcal (iGAS) infections in children was observed in Europe, including Germany and Switzerland. While a...
BACKGROUND
In winter 2022/2023, a resurgence of invasive group A streptococcal (iGAS) infections in children was observed in Europe, including Germany and Switzerland. While a simultaneous increase in consultations for scarlet fever and pharyngitis was reported in England, leading to the recommendation to treat any suspected GAS disease with antibiotics, guidelines in Germany and Switzerland remained unchanged. We aimed to investigate whether this policy was appropriate.
METHODS
We conducted a retrospective multicenter study of children hospitalized for invasive GAS disease between September 2022 and March 2023 in pediatric departments in Dresden and Berlin (Germany) and Basel (Switzerland). We reviewed medical records and conducted structured telephone interviews to analyze whether suspected GAS infections with or without antibiotic treatment were reported prehospitalization.
RESULTS
In total, 63 patients met the inclusion criteria (median age 4.2 years, 57% males); however, clinical information was not complete for all analyzed characteristics; 32/54 (59%) had ≥1 physician visit ≤4 weeks prehospitalization. In 4/32 (13%) patients, GAS disease, that is, tonsillitis or scarlet fever, was suspected; 2/4 of them received antibiotics, and a positive rapid antigen test for GAS was documented in 1 of them.
CONCLUSIONS
A small minority of patients had suspected GAS infection within 4 weeks before iGAS disease. These data suggest that there is little opportunity to prevent iGAS disease by antibiotic therapy, because in most patients-even if seen by a physician-there was either no evidence of GAS disease or when GAS disease was suspected and treated with antibiotics, consecutive invasive GAS disease was not prevented.
PubMed: 38830130
DOI: 10.1097/INF.0000000000004403 -
EClinicalMedicine Jul 2024Little is known about post-acute sequelae of SARS-CoV-2 infection (PASC) after acquiring SARS-CoV-2 infection during pregnancy. We aimed to evaluate the association...
BACKGROUND
Little is known about post-acute sequelae of SARS-CoV-2 infection (PASC) after acquiring SARS-CoV-2 infection during pregnancy. We aimed to evaluate the association between acquiring SARS-CoV-2 during pregnancy compared with acquiring SARS-CoV-2 outside of pregnancy and the development of PASC.
METHODS
This retrospective cohort study from the Researching COVID to Enhance Recovery (RECOVER) Initiative Patient-Centred Clinical Research Network (PCORnet) used electronic health record (EHR) data from 19 U.S. health systems. Females aged 18-49 years with lab-confirmed SARS-CoV-2 infection from March 2020 through June 2022 were included. Validated algorithms were used to identify pregnancies with a delivery at >20 weeks' gestation. The primary outcome was PASC, as previously defined by computable phenotype in the adult non-pregnant PCORnet EHR dataset, identified 30-180 days post-SARS-CoV-2 infection. Secondary outcomes were the 24 component diagnoses contributing to the PASC phenotype definition. Univariable comparisons were made for baseline characteristics between individuals with SARS-CoV-2 infection acquired during pregnancy compared with outside of pregnancy. Using inverse probability of treatment weighting to adjust for baseline differences, the association between SARS-CoV-2 infection acquired during pregnancy and the selected outcomes was modelled. The incident risk is reported as the adjusted hazard ratio (aHR) with 95% confidence intervals.
FINDINGS
In total, 83,915 females with SARS-CoV-2 infection acquired outside of pregnancy and 5397 females with SARS-CoV-2 infection acquired during pregnancy were included in analysis. Non-pregnant females with SARS-CoV-2 infection were more likely to be older and have comorbid health conditions. SARS-CoV-2 infection acquired in pregnancy as compared with acquired outside of pregnancy was associated with a lower incidence of PASC (25.5% vs 33.9%; aHR 0.85, 95% CI 0.80-0.91). SARS-CoV-2 infection acquired in pregnant females was associated with increased risk for some PASC component diagnoses including abnormal heartbeat (aHR 1.67, 95% CI 1.43-1.94), abdominal pain (aHR 1.34, 95% CI 1.16-1.55), and thromboembolism (aHR 1.88, 95% CI 1.17-3.04), but decreased risk for other diagnoses including malaise (aHR 0.35, 95% CI 0.27-0.47), pharyngitis (aHR 0.36, 95% CI 0.26-0.48) and cognitive problems (aHR 0.39, 95% CI 0.27-0.56).
INTERPRETATION
SARS-CoV-2 infection acquired during pregnancy was associated with lower risk of development of PASC at 30-180 days after incident SARS-CoV-2 infection in this nationally representative sample. These findings may be used to counsel pregnant and pregnant capable individuals, and direct future prospective study.
FUNDING
National Institutes of Health (NIH) Other Transaction Agreement (OTA) OT2HL16184.
PubMed: 38828129
DOI: 10.1016/j.eclinm.2024.102654 -
JMIR Research Protocols May 2024A dietary supplement containing Pelargonium sidoides extract, propolis, zinc, and honey has been recently developed and proven to be an effective adjuvant in clinical...
The Effects of a Dietary Supplement (PediaFlù) Plus Standard of Care in Children With Acute Tonsillopharyngitis/Rhinopharyngitis: Protocol for a Randomized Controlled Trial.
BACKGROUND
A dietary supplement containing Pelargonium sidoides extract, propolis, zinc, and honey has been recently developed and proven to be an effective adjuvant in clinical practice for seasonal diseases and the treatment of respiratory tract disorders.
OBJECTIVE
This trial aims to verify the efficacy of the tested dietary supplement in a pediatric population with acute tonsillopharyngitis/rhinopharyngitis (ATR).
METHODS
The trial includes children aged between 3 and 10 years with ATR ≤48 h, a negative rapid test for beta-hemolytic streptococcus or culture identification of nasal and/or pharyngeal exudates, and SARS-CoV-2 infection. The dietary supplement tested is an oral solution already on the market based on Pelagon P-70 (equivalent to Pelargonium sidoides d.e. 133.3 mg/100 ml), propolis, zinc, and honey. The product is administered at 5 ml 3 times a day for 6 days for children younger than 6 years and 10 ml 3 times a day for 6 days for children older than 6 years. The study design is open label, randomized, and controlled, with the tested dietary supplement plus standard of care (SoC) versus SoC alone. Patients are enrolled from 3 sites in Romania. The change in Tonsillitis Severity Score and number of treatment failures (using ibuprofen or high-dose paracetamol as rescue medication) are the primary end points. Based on the Tonsillitis Severity Score and the 2-sample comparison of the means formula with a 5% significance level, 80% power, and a minimally clinically important difference of 2 (SD 3.85) points, 120 patients are required. To account for potential screening failures and dropouts, we need to screen a population of approximately 150 children.
RESULTS
Patient enrollment began on June 3, 2021 (first patient's first visit), and ended on August 12, 2021 (last patient's last visit). The data collection period was from June 3, 2021, to September 16, 2021. The study was funded in February 2023. Data analysis is currently ongoing (April 2024). We expect the results to be published in a peer-reviewed clinical journal in the third quarter of 2024 and presented at scientific meetings in the last quarter of 2024.
CONCLUSIONS
The data from this trial may help identify new adjuvant treatments for children with ATR when streptococcal infection is excluded by a negative rapid test, thereby avoiding unnecessary antibiotic administration.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04899401 https://clinicaltrials.gov/study/NCT04899401.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/53703.
Topics: Child; Child, Preschool; Female; Humans; Male; Acute Disease; COVID-19; Dietary Supplements; Honey; Pharyngitis; Plant Extracts; Propolis; Randomized Controlled Trials as Topic; Standard of Care; Tonsillitis; Zinc
PubMed: 38819917
DOI: 10.2196/53703 -
MBio May 2024The hyaluronic acid capsule is crucial in protecting group A (GAS) against phagocytic killing. However, there have been reported outbreaks caused by capsule-deficient...
UNLABELLED
The hyaluronic acid capsule is crucial in protecting group A (GAS) against phagocytic killing. However, there have been reported outbreaks caused by capsule-deficient GAS strains, and the mechanisms underlying their evasion of immune clearance remain unclear. This study demonstrated that the capsule-deficient mutant [Cap(-)] of the strain increased survival within phagocytic cells compared to the wild-type strain [Cap(+)]. Although both Cap(+) and Cap(-) strains exhibited similar abilities to disrupt the phagosome, only the Cap(+) strain was colocalized with lysosomes and acidified compartments in phagocytic cells, indicating its susceptibility to autophagosome elimination. In contrast, the Cap(-) mutant evaded the recognition of galectin-8 and ubiquitin, impairing selective autophagy-mediated elimination. These findings suggest that a deficiency in the capsule could impair the intracellular elimination of GAS in macrophages, revealing previously unknown aspects of the host's recognition of the GAS capsule in macrophages.
IMPORTANCE
Group A (GAS) is a Gram-positive bacterium that causes diseases ranging from mild pharyngitis to severe necrotizing fasciitis. Phagocytic cells serve as the primary defense against bacterial infections, exhibiting remarkable efficiency in eliminating intracellular pathogens. The hyaluronic acid capsule is a critical virulence factor that contributes to the resistance of phagocytosis in GAS. Nevertheless, the outbreaks caused by GAS strains that lack the hyaluronic acid capsule have been reported, and the selective advantage of capsule-deficient strains during infection is not fully understood. This study showed that the autophagic adaptor proteins recognize the capsulated GAS strain but not the capsule-deficient mutant, indicating that the hyaluronic acid capsule could be the autophagic target in macrophages. These findings imply that the hyaluronic acid capsule of GAS actually enhances its elimination within phagocytic cells, subverting the understanding of the capsule in GAS pathogenesis.
PubMed: 38819157
DOI: 10.1128/mbio.00771-24 -
Vestnik Otorinolaringologii 2024The results of a prospective open cohort study of the use of platelet-rich plasma (platelet-rich plasma - PRP) in patients with chronic pharyngitis during the...
UNLABELLED
The results of a prospective open cohort study of the use of platelet-rich plasma (platelet-rich plasma - PRP) in patients with chronic pharyngitis during the exacerbation of the disease are presented.
OBJECTIVE
To evaluate the clinical efficacy of autologous PRP in the treatment of chronic pharyngitis.
MATERIAL AND METHODS
Autologous PRP was injected into the posterior pharyngeal wall as a course of endopharyngeal blockages as part of the complex therapy of chronic pharyngitis. Patients in the control group received standard therapy, without the use of autologous PRP. The effectiveness of the studied technique was evaluated by statistical analysis of the intensity of symptoms of the disease, determined by patients throughout the entire period of treatment in the patient's diary, as well as by analyzing data from mass spectrometry of microbial markers and bacteriological examination of the pharyngeal mucosa, collected at the beginning of the study and 14 days after completion of the course of therapy.
CONCLUSION
The use of a course of endopharyngeal blockades with autologous platelet-rich plasma as part of the complex therapy of chronic pharyngitis, according to our estimates, provides a significant effect in the form of higher rates of reduction in the severity of symptoms of the disease, a significant reduction in the number of microorganisms deviating from the reference values (by 2 times or more), a decrease in the duration of the disease compared with the control group.
Topics: Humans; Platelet-Rich Plasma; Pharyngitis; Female; Male; Adult; Chronic Disease; Treatment Outcome; Middle Aged; Prospective Studies; Blood Transfusion, Autologous
PubMed: 38805464
DOI: 10.17116/otorino20248902152 -
Frontiers in Cardiovascular Medicine 2024Rheumatic heart disease (RHD) is a preventable sequelae of group A beta hemolytic streptococcal infection leading to an immune reaction: acute rheumatic fever (ARF) and... (Review)
Review
BACKGROUND
Rheumatic heart disease (RHD) is a preventable sequelae of group A beta hemolytic streptococcal infection leading to an immune reaction: acute rheumatic fever (ARF) and progressive heart valve dysfunction. RHD is the leading cause of acquired heart disease in children and young adults in Sudan and many low/middle-income countries. In 2018, the World Health Organization (WHO) issued a resolution for RHD mandating that each country adopt updated guidelines for ARF and RHD management. These current guidelines are mainly directed to primary healthcare workers.
METHODS
Sudan's Federal Ministry of Health (FMOH) in collaboration with the WHO East Mediterranean Regional Office (EMRO) assembled a committee for updating RHD guidelines. We conducted a systematic literature search from 2000 to 2022 in National Institute of Health Database (PubMed) under the following titles: streptococcal pharyngitis, acute rheumatic fever, rheumatic heart disease, benzathine penicillin. Best available, evidence-based practices for diagnosis and management of ARF/RHD were selected and adapted to Sudan's situation. The guidelines were critically appraised by the committee then endorsed to the FMOH and WHO EMRO Noncommunicable Disease Departments in January 2023. This paper describes the updated guidelines.
RESULTS
Simplified algorithms are provided for diagnosis of bacterial pharyngitis including two clinical criteria: sore throat and the absence of viral symptoms in the target age group. A simplified algorithm for diagnosis and management of ARF is adopted using two levels of diagnosis: suspected case at primary level where penicillin prophylaxis is started and secondary/tertiary care where echocardiography is performed and diagnosis confirmed or excluded. Echocardiography screening is recognized as the standard method for early diagnosis of RHD; however, due to the anticipated limitations, its implementation was not adopted at this time. Streptococcal skin infection is included as a precursor of ARF and a detailed protocol for benzathine penicillin administration is described.
CONCLUSION
The Sudan guidelines for ARF/RHD management were updated. Endorsement of these guidelines to FMOH and WHO EMRO is expected to improve control of RHD in the region.
PubMed: 38798925
DOI: 10.3389/fcvm.2024.1403131 -
International Journal of Molecular... May 2024Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying...
Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying mechanisms supporting tonsillectomy remain unclear. This study assessed palatine tonsils from 77 patients with IgAN, including 14 and 63 who received SPT before and after tonsillectomy, respectively. Tonsils from 21 patients with chronic tonsillitis were analyzed as controls. Specific tonsillar lesions were confirmed in patients with IgAN, correlating with active or chronic renal glomerular lesions and SPT. T-nodule and involution of lymphoepithelial symbiosis scores in tonsils correlated with the incidence of active crescents and segmental sclerosis in the glomeruli, respectively. The study revealed an essential role of the tonsil-glomerular axis in early active and late chronic phases. Moreover, the SPT-preceding group demonstrated no changes in the T-nodule score, which correlated with active crescent formation, but exhibited a considerable shrinkage of lymphatic follicles that produced aberrant IgA1. The study underscores the involvement of innate and cellular immunity in IgAN and advocates for tonsillectomy as a necessary treatment alongside SPT for IgAN, based on a stepwise process.
Topics: Humans; Glomerulonephritis, IGA; Tonsillectomy; Palatine Tonsil; Female; Male; Adult; Kidney Glomerulus; Retrospective Studies; Middle Aged; Tonsillitis; Young Adult; Immunoglobulin A
PubMed: 38791337
DOI: 10.3390/ijms25105298 -
Pathogens (Basel, Switzerland) Apr 2024Group A Streptococcus (GAS) presents a significant global health burden due to its diverse clinical manifestations ranging from mild infections to life-threatening... (Review)
Review
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.
PubMed: 38787202
DOI: 10.3390/pathogens13050350 -
Toxics May 2024Oridonin is the primary active component in the traditional Chinese medicine , displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed...
Oridonin is the primary active component in the traditional Chinese medicine , displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, β-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/β-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.
PubMed: 38787118
DOI: 10.3390/toxics12050339 -
Talanta Aug 2024Streptococcus pyogenes (Group A Streptococcus; GAS) is a Gram-positive bacterium responsible for substantial human mortality and morbidity. Conventional diagnosis of GAS...
Streptococcus pyogenes (Group A Streptococcus; GAS) is a Gram-positive bacterium responsible for substantial human mortality and morbidity. Conventional diagnosis of GAS pharyngitis relies on throat swab culture, a low-throughput, slow, and relatively invasive 'gold standard'. While molecular approaches are becoming increasingly utilized, the potential of saliva as a diagnostic fluid for GAS infection remains largely unexplored. Here, we present a novel, high-throughput, sensitive, and robust speB qPCR assay that reliably detects GAS in saliva using innovative 3base™ technology (Genetic Signatures Limited, Sydney, Australia). The assay has been validated on baseline, acute, and convalescent saliva samples generated from the Controlled Human Infection for Vaccination Against Streptococcus (CHIVAS-M75) trial, in which healthy adult participants were challenged with emm75 GAS. In these well-defined samples, our high-throughput assay outperforms throat culture and conventional qPCR in saliva respectively, affirming the utility of the 3base™ platform, demonstrating the feasibility of saliva as a diagnostic biofluid, and paving the way for the development of novel non-invasive approaches for the detection of GAS and other oropharyngeal pathogens.
Topics: Humans; Streptococcus pyogenes; Saliva; Pharyngitis; Streptococcal Infections; Adult; Real-Time Polymerase Chain Reaction
PubMed: 38776768
DOI: 10.1016/j.talanta.2024.126221