Efficacy of Alum-Adjuvanted Peptide and Carbohydrate Conjugate Vaccine Candidates against Group A Streptococcus Pharyngeal Infection in a Non-Human Primate Model.

Vaccine development against group A Streptococcus (GAS) has gained traction in the last decade, fuelled by recognition of the significant worldwide burden of the disease. Several vaccine candidates are currently being evaluated in preclinical and early clinical studies. Here, we investigate two conjugate vaccine candidates that have shown promise in mouse models of infection. Two antigens, the J8 peptide from the conserved C-terminal end of the M protein, and the group A carbohydrate lacking N-acetylglucosamine side chain (ΔGAC) were each conjugated to arginine deiminase (ADI), an anchorless surface protein from GAS. Both conjugate vaccine candidates combined with alum adjuvant were tested in a non-human primate (NHP) model of pharyngeal infection. High antibody titres were detected against J8 and ADI antigens, while high background antibody titres in NHP sera hindered accurate quantification of ΔGAC-specific antibodies. The severity of pharyngitis and tonsillitis signs, as well as the level of GAS colonisation, showed no significant differences in NHPs immunised with either conjugate vaccine candidate compared to NHPs in the negative control group.

Neurologic complications of rheumatic fever.

Sydenham chorea, also known as St. Vitus dance, is a major clinical criterion for the diagnosis of acute rheumatic fever. Clinically, it results in a combination of movement disorders and complex neuropsychiatric symptoms. Cardiac damage due to rheumatic fever may also predispose to neurologic complications later in life. Rheumatic heart disease (RHD) is associated with heart remodeling, cardiac arrhythmias, and ischemic stroke. Furthermore, chronically damaged heart valves are predisposed to infection. Septic brain embolism, a known complication of infective endocarditis, may result in brain ischemia, hemorrhage, and spread of the infection to the brain.

Humanized Plasminogen Mouse Model to Study Group A Streptococcus Invasive Disease.

This chapter presents the methodology to carry out infection of humanized plasminogen mice with Group A Streptococcus (GAS). This model of invasive disease has been widely used within the field to study the virulence of different GAS strains, host-pathogen interactions, the importance of particular virulence factors, and preclinical evaluation of novel treatments and vaccines. The model has shown to be highly reproducible and therefore represents an invaluable tool for GAS research.

Identifying Patients at Lowest Risk for Streptococcal Pharyngitis: A National Validation Study.

OBJECTIVES: To determine the prevalence of features of viral illness in a national sample of visits involving children tested for group A Streptococcus pharyngitis. Additionally, we sought to derive a decision rule to identify patients with features of viral illness who were at low risk of having group A Streptococcus and for whom laboratory testing might be avoided. STUDY DESIGN: Retrospective validation study using data from electronic health records of patients 3-21 years old evaluated for sore throat in a national network of retail health clinics (n = 67 127). We determined the prevalence of features of viral illness in patients tested for group A Streptococcus and developed a decision tree algorithm to identify patients with features of viral illness at low risk (<15%) of having group A Streptococcus. RESULTS: Overall, 54% of patients had features of viral illness. Among patients with features of viral illness, those without tonsillar exudates who were 11 years or older and either lacked cervical adenopathy or had cervical adenopathy and lacked fever were identified as at low risk for group A Streptococcus according to the decision rule. This group comprised 34% of patients with features of viral illness, or 19% of all patients tested for group A Streptococcus infection. CONCLUSIONS: Our findings provide an objective way to identify patients with features of viral illness who are at low risk of having group A Streptococcus. Improved identification such patients at low risk of group A Streptococcus could improve appropriate testing and antibiotic prescribing for pharyngitis.

Prevalence of group a Beta-hemolytic streptococcus oropharyngeal colonization in children and therapeutic regimen based on antistreptolysin levels: data from a city from southern Brazil.

The aim of this study is to determinate the prevalence of oropharyngeal colonization by group A beta-hemolytic Streptococcus (GABHS) in pediatric population of Ponta Grossa, a midsize city of southern Brazil; estimate the effectiveness of antistreptolysin-O (ASO), compared to culture, in presence of infection; and design an unpublished investigative algorithm of rheumatic fever's suspicion, based on needs identified in worldwide consensus. It is an epidemiologic, observational and transversal study, involving 180 children younger than 12 years. Secretion of posterior oropharynx was collected for culture; and peripheral blood for determination of ASO. Student-t and chi-square tests, with Yates correction, were performed for statistical analysis. The ASO cutoff was determined by Receiver Operating Characteristic (ROC) curve. The prevalence encountered was 3.9%, and 25.5% of the children showed reagent ASO. This serological test demonstrated quantitatively and qualitatively significant associations to the GABHS presence (p=0.0001 for both associations) throughout the ROC curve, 200 U Todd was the value that resulted in the best accuracy, demonstrating 100% of sensibility and 80% of specificity in the GAS infection documentation. Also, it was found that the value of 1.200 U represents a specificity of 100%. The results emphasize the need for similar studies in other populations, to provide better targeting of the diagnosis and treatment of oropharyngitis by GABHS, which in turn can prevent up to 80% the cases of rheumatic fever, and consequently, the chronic rheumatic heart disease.