Using Implementation Mapping to develop an intervention program to support veterinarians' adherence to the guideline on Streptococcus suis clinical practice in weaned pigs.

Streptococcus suis (S. suis) infections in weaned pigs are common and responsible for a high consumption of antimicrobials, and their presence is assumed to be multi-factorial. A specific evidence-based veterinary guideline to support the control of S. suis in weaned pigs was developed for veterinary practitioners in the Netherlands in 2014. Adherence to the S. suis clinical practice guideline helps veterinary practitioners to prevent and control the disease in a systematical approach and thereby improve antimicrobial stewardship and contribute to the prevention of antimicrobial resistance in animals and humans. The impact of such a clinical practice guideline on (animal) disease management depends not only on its content, but also largely on the extent to which practitioners adhere to the clinical guideline in practice. When the S. suis guideline was published, no specific activities were undertaken to support veterinarians' uptake and implementation, thereby contributing to suboptimal adherence in clinical practice. As the S. suis guideline was comprehensively written by veterinary experts following an evidence-based approach, our aim was not to judge the (scientific) quality of the guideline but to study the possibility to improve the currently low adherence of this guideline in veterinary practice. This paper describes the systematic development, using Implementation Mapping, of a theory-based intervention program to support swine veterinarians' adherence to the S. suis guideline. The knowledge, skills, beliefs about capabilities, and beliefs about consequences domains are addressed in the program, which includes seven evidence-based methods (modelling, tailoring, feedback, discussion, persuasive communication, active learning, and self-monitoring) for use in program activities such as a peer-learning meeting and an e-learning module. The intervention program has been developed for practicing swine veterinarians, lasts eight months, and is evaluated through a stepped-wedge design. The Implementation Mapping approach ensured that all relevant adopters and implementers were involved, and that outcomes, determinants (influencing factors), and objectives were systematically discussed.

Application of Transthoracic Echocardiography for Cardiac Safety Evaluation in the Clinical Development Process of Vaccines Against Streptococcus pyogenes.

Superficial infections with Streptococcus pyogenes (Strep A), pharyngitis and impetigo can induce acute rheumatic fever, an autoimmune sequela manifesting mostly with arthritis and rheumatic carditis. Valvular heart damage can persist or advance following repeated episodes of acute rheumatic fever, causing rheumatic heart disease. Acute rheumatic fever and rheumatic heart disease disproportionately affect children and young adults in developing countries and disadvantaged communities in developed countries. People living with rheumatic heart disease are at risk of experiencing potentially fatal complications such as heart failure, bacterial endocarditis or stroke. Transthoracic echocardiography plays a central role in diagnosing both rheumatic carditis and rheumatic heart disease. Despite the obvious medical need, no licensed Strep A vaccines are currently available, as their clinical development process faces several challenges, including concerns for cardiac safety. However, the development of Strep A vaccines has been recently relaunched by many vaccine developers. In this context, a reliable and consistent safety evaluation of Strep A vaccine candidates, including the use of transthoracic echocardiography for detecting cardiac adverse events, could greatly contribute to developing a safe and efficacious product in the near future. Here, we propose a framework for the consistent use of transthoracic echocardiography to proactively detect cardiac safety events in clinical trials of Strep A vaccine candidates.

Throat and skin infections caused by certain types of bacteria, named Streptococcus pyogenes, are frequent worldwide; however, in many children from less developed countries and disadvantaged communities, infections with S. pyogenes lead to a condition called acute rheumatic fever, which usually affects the joints and the heart. Damage to the heart valves may evolve to rheumatic heart disease, a permanent condition with often life-threatening complications. Rheumatic heart disease is an important health problem in places and communities where S. pyogenes infections occur frequently. A vaccine against these bacteria would help lower the number of people with valvular heart disease; however, no such vaccine exists yet. Research on vaccines against S. pyogenes was on hold for almost 30 years because of initial concerns that vaccinated children might develop acute rheumatic fever more frequently. Recently, researchers started working again on vaccines against S. pyogenes, but concerns about the safety of such vaccines persist. Doctors can reliably use echocardiography to diagnose cases of rheumatic carditis (as a sign of acute rheumatic fever) and rheumatic heart disease. Here, we propose a simple approach for the consistent use of echocardiography in clinical research of vaccines against S. pyogenes that will allow the detection of any potential heart-related side effects of the vaccine.

Preventive Interventions to Reduce the Burden of Rheumatic Heart Disease in Populations at Risk: A Systematic Review.

BACKGROUND: Rheumatic heart disease (RHD) is a devastating yet preventable condition that disproportionately affects low-middle-income countries and indigenous populations in some high-income countries. Various preventive interventions have been implemented across the globe, but evidence for the effectiveness of these measures in reducing the incidence or prevalence of acute rheumatic fever and RHD is scattered. This systematic review aims to assess the effectiveness of preventive interventions and identify the strategies used to reduce the burden of RHD. METHODS AND RESULTS: A comprehensive search was conducted to identify relevant studies on RHD prevention interventions including interventions for primordial, primary, and secondary prevention. Effectiveness measures for the interventions were gathered when available. The findings indicate that school-based primary prevention services targeting the early detection and treatment of Group A Streptococcus pharyngitis infection with penicillin have the potential to reduce the incidence of Group A Streptococcus pharyngitis and acute rheumatic fever. Community-based programs using various prevention strategies also reduced the burden of RHD. However, there is limited evidence from low-middle-income countries and a lack of rigorous evaluations reporting the true impact of the interventions. Narrative synthesis was performed, and the methodological quality appraisal was done using the Joanna Briggs Institute critical appraisal tools. CONCLUSIONS: This systematic review underscores the importance of various preventive interventions in reducing the incidence and burden of Group A Streptococcus pharyngitis, acute rheumatic fever, and RHD. Rigorous evaluations and comprehensive analyses of interventions are necessary for guiding effective strategies and informing public health policies to prevent and reduce the burden of these diseases in diverse populations. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42020170503.

"Why has this new vaccine come and for what reasons?" key antecedents and questions for acceptance of a future maternal GBS vaccine: Perspectives of pregnant women, lactating women, and community members in Kenya.

Group B streptococcus (GBS) is a leading global cause of neonatal sepsis and meningitis, stillbirth, and puerperal sepsis. While intrapartum antibiotic prophylaxis (IAP) is a currently available GBS disease prevention strategy, IAP is programmatically complex to implement, precluding use in low- and middle-income countries. In Kenya, 2% of stillbirths are attributable to GBS infection. Two maternal GBS vaccines are in late-stage clinical development. However, licensure of a maternal GBS vaccine does not translate into reduction of disease. We conducted 28 in-depth interviews with pregnant people, lactating people, and community members across two counties in Kenya to better understand the attitudes and informational needs of primary vaccine beneficiaries. We identified two emerging themes from the data. The first focused on antecedents to maternal GBS vaccine acceptability. The most common antecedents focused on the vaccine's ability to protect the baby and/or the mother, followed by community sensitization before the vaccine was available. The second key theme focused on questions that would need to be addressed before someone could accept a maternal GBS vaccine. Three key categories of questions were identified, including vaccine safety compared to vaccine benefits, who gets the vaccine, and how the vaccine works. Realizing the potential benefits of a future GBS maternal vaccine will require a multifactorial approach, including ensuring that communities are aware of GBS-related harms as well as the safety and effectiveness of a maternal GBS vaccine. Our study contributes to informing this multifactorial approach by elucidating the attitudes and concerns of key populations.

Oral Probiotic Supplementation in Pregnancy to Reduce Group B Streptococcus Colonisation (OPSiP trial): study protocol for a double-blind parallel group randomised placebo trial.

INTRODUCTION: Group B streptococcus (GBS), or Streptococcus agalactiae, remains a leading cause of neonatal morbidity and mortality. Canadian guidelines advise universal maternal screening for GBS colonisation in pregnancy in conjunction with selective antibiotic therapy. This results in over 1000 pregnant individuals receiving antibiotic therapy to prevent one case of early-onset neonatal GBS disease, and over 20 000 pregnant individuals receiving antibiotic therapy to prevent one neonatal death. Given the growing concern regarding the risk of negative sequela from antibiotic exposure, it is vital that alternative approaches to reduce maternal GBS colonisation are explored.Preliminary studies suggest some probiotic strains could confer protection in pregnancy against GBS colonisation. METHODS AND ANALYSIS: This double-blind parallel group randomised trial aims to recruit 450 pregnant participants in Vancouver, BC, Canada and will compare GBS colonisation rates in those who have received a daily oral dose of three strains of probiotics with those who have received a placebo. The primary outcome will be GBS colonisation status, measured using a vaginal/rectal swab obtained between 35 weeks' gestation and delivery. Secondary outcomes will include maternal antibiotic exposure and urogenital infections. Analysis will be on an intention-to-treat basis. PATIENT OR PUBLIC INVOLVEMENT: There was no patient or public involvement in the design of the study protocol. ETHICS AND DISSEMINATION: This study protocol received ethics approval from the University of British Columbia's Clinical Research Ethics Board, Dublin City University and Health Canada. Findings will be presented at research rounds, conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03407157.

Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Group B Streptococcal Disease in Infants in Japan.

This review describes the epidemiology of group B Streptococcus (GBS) infection in infants in Japan and discusses unresolved issues and future perspectives. Guidelines for the prevention of vertical transmission in Japan were implemented in 2008. The incidence of early-onset disease in Japan has remained stable at approximately 0.10/1000 livebirths or less, which is lower than in Europe and North America. The incidence of late-onset disease is also low, but has increased over the last decade, with an estimated 0.29/1000 livebirths in 2020. National surveillance studies in 2011-2015 and 2016-2020 reported case fatality rates of 4.5% and 6.5% for early-onset disease and 4.4% and 3.0% for late-onset disease, respectively. Sequelae of neurodevelopmental impairments were considerably associated with infants who developed meningitis. Predominant neonatal invasive strains have remained in the following order of serotypes: III, Ia, Ib and V, for the past 30 years. Conversely, the predominant serotypes of maternal colonization strains markedly changed from serotypes VI and VIII around 2000 to serotypes Ia, Ib, III and V over the last decade. Recurrence rates among infants < 1-year-old were estimated to be 2.8%-3.7%, and preterm birth and antenatal maternal GBS colonization were risk factors for recurrence. Several unresolved issues remain. First, the exact disease burden remains unclear because Japan does not have a nationwide system to register all infants affected by invasive GBS disease, and even population-based surveys are limited to up to 10 of the 47 prefectures. Others include low adherence to prevention guidelines of vertical transmission and the development of strategies based on Japanese epidemiological evidence rather than the Center for Disease Control and Prevention guidelines. The effectiveness of introducing maternal vaccines in Japan, where the disease incidence is low, needs to be carefully verified.

A nanocarrier immersion vaccine encoding surface immunogenic protein confers cross-immunoprotection against Streptococcus agalactiae and Streptococcus iniae infection in tilapia.

Streptococcosis is a highly contagious aquatic bacterial disease that poses a significant threat to tilapia. Vaccination is a well-known effective measure to prevent and control fish bacterial diseases. Among the various immunization methods, immersion vaccination is simple and can be widely used in aquaculture. Besides, nanocarrier delivery technology has been reported as an effective solution to improve the immune effect of immersion vaccine. In this study, the surface immunogenic protein (Sip) was proved to be conserved and potential to provide cross-immunoprotection for both Streptococcus agalactiae (S. agalactiae) and Streptococcus iniae (S. iniae) by multiple sequences alignment and Western blotting analysis. On this basis, we expressed and obtained the recombinant protein rSip and connected it with functionalized carbon nanotubes (CNT) to construct the nanocarrier vaccine system CNT-rSip. After immersion immunization, the immune effect of CNT-rSip against above two streptococcus infections was evaluated in tilapia based on some aspects including the serum specific antibody level, non-specific enzyme activities, immune-related genes expression and relative percent survival (RPS) after bacteria challenge. The results showed that compared with control group, CNT-rSip significantly (P < 0.05) increased the serum antibody levels, related enzyme activities including acid phosphatase, alkaline phosphatase, lysozyme and total antioxidant capacity activities, as well as the expression levels of immune-related genes from 2 to 4 weeks post immunization (wpi), and all these indexes peaked at 3 wpi. Besides, the above indexes of CNT-rSip were higher than those of rSip group with different extend during the experiment. Furthermore, the challenge test indicated that CNT-rSip provided cross-immunoprotection against S. agalactiae and S. iniae infection with RPS of 75 % and 72.41 %, respectively, which were much higher than those of other groups. Our study indicated that the nanocarrier immersion vaccine CNT-rSip could significantly improve the antibody titer and confer cross-immuneprotection against S. agalactiae and S. iniae infection in tilapia.

Efficacy of whole-cell-based monovalent and bivalent vaccines against Streptococcus iniae and Flavobacterium covae in fingerling Asian seabass (Lates calcarifer).

Streptococcosis and columnaris caused by Streptococcus spp. and Flavobacterium spp. have been recognized as critical problems in Asian seabass aquaculture development because they cause severe mortality. In this study, we identified various isolates of S. iniae and F. covae from diseased Asian seabass farmed in Thailand for use as candidates for vaccine development. The efficacy of the vaccines was evaluated by challenge tests and immune parameter analyses in fish that received whole-cell-based monovalent and bivalent vaccines containing S. iniae (Sin) and F. covae (Fco) delivered by top-dressed feed (TD) and intraperitoneal injection (IP). The results showed that all vaccinated groups exhibited increased antibody titers compared with control fish that peaked on day 28 after booster administration with high detection levels in the Sin-IP and Fco-IP groups. Moreover, the immune responses to the injected monovalent vaccines (Sin-IP and Fco-IP) were better than the responses in the other vaccinated groups. The hematological and innate immunological parameters were significantly increased by Sin-IP and Fco-IP, particularly lysozyme activity, nitroblue tetrazolium (NBT) activity, bactericidal activity, and white blood cell numbers, and immune-related genes, including IgM, MHC-IIα, TCRß and CD4, were significantly upregulated in the head kidney, whole blood and spleen (P < 0.05). After experimental challenge, survival in the Sin-IP and Fco-IP groups was significantly higher than that in the Sin-TD, Fco-TD, Sin + Fco-TD, and Sin + Fco-IP groups, with 80.0 % and 60.0 % survival after S. iniae and F. covae infection, respectively. In contrast, survival after bacterial challenge in the control groups was 10 % in each group. Histopathological analysis revealed that Sin-IP- and Fco-IP-vaccinated fish exhibited significantly more goblet cells in the intestines and melanomacrophage centers (MMCs) in the head kidney and spleen than those in the other groups (P < 0.05). Overall, the results of our study indicated that the monovalent vaccines Sin-IP and Fco-IP provoked better vaccine efficacy and immune responses than their orally administered counterparts, and these results are consistent with those from the immunological assays that showed significantly increased responses after immunization.

Global Streptococcus pyogenes strain diversity, disease associations, and implications for vaccine development: a systematic review.

The high strain diversity of Streptococcus pyogenes serves as a major obstacle to vaccine development against this leading global pathogen. We did a systematic review of studies in PubMed, MEDLINE, and Embase that reported the global distribution of S pyogenes emm-types and emm-clusters from Jan 1, 1990, to Feb 23, 2023. 212 datasets were included from 55 countries, encompassing 74 468 bacterial isolates belonging to 211 emm-types. Globally, an inverse correlation was observed between strain diversity and the UNDP Human Development Index (HDI; r=-0·72; p<0·0001), which remained consistent upon subanalysis by global region and site of infection. Greater strain diversity was associated with a lower HDI, suggesting the role of social determinants in diseases caused by S pyogenes. We used a population-weighted analysis to adjust for the disproportionate number of epidemiological studies from high-income countries and identified 15 key representative isolates as vaccine targets. Strong strain type associations were observed between the site of infection (invasive, skin, and throat) and several streptococcal lineages. In conclusion, the development of a truly global vaccine to reduce the immense burden of diseases caused by S pyogenes should consider the multidimensional diversity of the pathogen, including its social and environmental context, and not merely its geographical distribution.

Correlation of Streptococcus agalactiae concentration on immune system and effective dose of inactivated vaccine for Chitralada 3 strain Nile tilapia (Oreochromis niloticus) in Thailand.

The main pathogen in the Nile tilapia (Oreochromis niloticus) culture, Streptococcus agalactiae, causes economic harm. Infected fish's immune systems worked to eliminate of the infection. This study demonstrated the effect of different bacterial concentrations on tilapia immunity and optimal vaccine concentration to induce immunity in Nile tilapia. The experiment was performed at 102, 104, 106, 108, and 1010 CFU/fish of S. agalactiae compared with the control (PBS) through intraperitoneal injection for 72 h. Fish that survived employed to gather blood, and immune responses were assessed through measures of the survival rate include blood smears, antibody titers, and immunoglobulin gene expression. The vaccine experiment investigated formalin-inactivated S. agalactiae vaccination and administered S. agalactiae injections for 14 days. The statistic revealed a significant difference (p < 0.05) in the 108 and 1010 CFU/fish injections with high survival rates (62.22% and 53.33%, respectively). Immunoglobulin gene expression was highly represented in the 1010 CFU/fish injection; antibody titers were significantly improved from the control group, and antibody levels were high in the 1010 CFU/fish injection. The analysis of blood cell types using the blood smear method revealed a progressive increase in leucocytes, particularly lymphocytes, neutrophils, and monocytes, in the treatment group compared to the control group. Moreover, the erythrocyte/leucocyte ratio decreased significantly in response to the high bacterial injection, indicating an increase in leucocytes. Conversely, the erythrocyte level stayed ed within at the 7.03-9.70 × 102 cell/ml and shown no significant difference (p > 0.05). The lymphocytes were almost two-fold in 1010 CFU/fish compared to 108 CFU/fish. As depicted in the lowest concentration of 106 CFU/fish, the vaccine performance had a high relative percent survival (RPS) at 86.67%. This research suggested that the tilapia infected with high S. agalactiae concentrations did not affect the mortality of the tilapia, and vaccine concentration was effective in 106 CFU/fish.

Prevention of Early-Onset Neonatal Group B Streptococcal Disease: A Comprehensive Review of Major Guidelines.

Importance: Group B Streptococcus (GBS) colonization during pregnancy is associated with significant neonatal morbidity and mortality and represents a major public health concern, often associated with poor screening and management. Objective: The aim of this study was to review and compare the most recently published influential guidelines on the screening and management of this clinical entity during antenatal and intrapartum periods. Evidence Acquisition: A descriptive review of guidelines from the American College of Obstetricians and Gynecologists, the Royal College of Obstetricians and Gynecologists, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, and the Society of Obstetricians and Gynecologists of Canada on the prevention of early-onset neonatal group B streptococcal disease was carried out. Results: There is a consensus among the reviewed guidelines regarding the optimal screening specimen type, indications for intrapartum antibiotic administration such as bacteriuria during pregnancy, clinical signs of chorioamnionitis or maternal pyrexia, and history of GBS-related neonatal disease. There is also agreement on several conditions where no intervention is recommended, that is, antepartum treatment of GBS and GBS-positive women with planned cesarean delivery and intact membranes. Controversy exists regarding the optimal screening time, with the Royal College of Obstetricians and Gynecologists stating against routine screening and on management strategies related to preterm labor and preterm prelabor rupture of membranes. Conclusions: The development of consistent international practice protocols for the timely screening of GBS and effective management of this clinical entity both during pregnancy and the intrapartum period seems of paramount importance to safely guide clinical practice and subsequently improve neonatal outcomes.

Vaccine value profile for Group B streptococcus.

Group B streptococcus (GBS) is a major global cause of neonatal meningitis, sepsis and pneumonia, with an estimated 91,000 infant deaths per year and an additional 46,000 stillbirths. GBS infection in pregnancy is also associated with adverse maternal outcomes and preterm births. As such, the World Health Organization (WHO) prioritised the development of a GBS vaccine suitable for use in pregnant women and use in LMICs, where the burden of disease is highest. Several GBS vaccines are in clinical development. The WHO Defeating Meningitis by 2030 has set a target of 2026 for vaccine licensure. This 'Vaccine Value Profile' (VVP) for GBS is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO regions of AFR, AMR, EUR, WPR. All contributors have extensive expertise on various elements of the GBS VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Effect of killed autogenous polyvalent vaccines against Vibrio harveyi, V. alginolyticus and Streptococcus iniae on survival and immunogenicity of Asian seabass (Latescalcarifer).

Vibriosis and Streptococcosis are the most important bacterial diseases that infect Asian seabass (Lates calcarifer) in various stages of its life cycle. Vaccination is a cost-effective strategy to prevent the occurrence of infectious diseases and increase sustainability in the aquaculture industry. This study was aimed to develop and evaluate a killed polyvalent vaccine against Vibrio harveyi, V. alginolyticus and Streptococcus iniae, delivered by intraperitoneal injection in Asian seabass. The fish were divided into three groups with 60 fish in triplicate: I) a control group injected with phosphate-buffered saline (PBS), II) a group vaccinated by polyvalent vaccine (V. alginolyticus + V. harveyi + S. iniae) and III) a group vaccinated with the same polyvalent vaccine plus an oral booster. Immunological parameters and antibody titer were measured before and at three, five-, and eight-weeks post-vaccination. The efficacy of the killed vaccine was assessed five weeks post-vaccination by challenging with each isolate separately. The vaccinated groups had higher survival rate than control group. The highest relative percentage survival rate, 85.71 ± 3.57 % was observed in group III when challenged with V. harveyi. The vaccinated fish produced significantly higher antibody titers against V. alginolyticus, V. harveyi and S. iniae than the control group (P < 0.05). Non-specific immune parameters were significantly enhanced in the vaccinated groups, especially group III, compared to the control. The results demonstrated that the administration of a killed polyvalent vaccine can effectively protect Asian seabass against V. alginolyticus, V. harveyi and S. iniae.

Antibiotic consumption for sore throat and the potential effect of a vaccine against group A Streptococcus: a systematic review and modelling study.

BACKGROUND: Antibiotic consumption can lead to antimicrobial resistance and microbiome imbalance. We sought to estimate global antibiotic consumption for sore throat, and the potential reduction in consumption due to effective vaccination against group A Streptococcus (Strep A). METHODS: We reviewed and analysed articles published between January 2000 and February 2022, identified though Clarivate Analytics' Web of Science search platform, with reference to antibiotic prescribing or consumption, sore throat, pharyngitis, or tonsillitis. We then used those analyses, combined with assumptions for the effectiveness, duration of protection, and coverage of a vaccine, to calculate the estimated reduction in antibiotic prescribing due to the introduction of Strep A vaccines. FINDINGS: We identified 101 studies covering 38 countries. The mean prescribing rate for sore throat was approximately 5 courses per 100 population per year, accounting for approximately 5% of all antibiotic consumption. Based on 2020 population estimates for countries with empiric prescribing rates, antibiotic consumption for sore throat was estimated to exceed 37 million courses annually, of which half could be attributable to treatment for Strep A. A vaccine that reduces rates of Strep A infection by 80%, with 80% coverage and 10 year's duration of protection, could avert 2.8 million courses of antibiotics prescribed for sore throat treatment among 5-14 year-olds in countries with observed prescribing rates, increasing to an estimated 7.5 million averted if an effective vaccination program also reduced precautionary prescribing. INTERPRETATION: A vaccine that prevents Strep A throat infections in children may reduce antibiotic prescribing for sore throat by 32-87% depending on changes to prescribing and consumption behaviours. FUNDING: The Wellcome Trust, grant agreement number 215490/Z/19/Z.

BNC-rSS, a bivalent subunit nanovaccine affords the cross-protection against Streptococcus agalactiae and Streptococcus iniae infection in tilapia.

Streptococcal disease has severely restricted the development of global tilapia industry, which is mainly caused by Streptococcus agalactiae (S. agalactiae) and Streptococcus iniae (S. iniae). Vaccination has been proved to be a potential strategy to control it. In this study, a multi-epitope subunit vaccine Sip-Srr (SS) was prepared based on the B-cell antigenic epitopes prediction and multiple sequence alignment analysis of Sip and Srr sequences. Furthermore, the BNC-rSS nanocarrier vaccine system was constructed by connecting the rSS protein with modified bacterial nanocellulose (BNCs) and characterized by Fourier Transform Infrared Spectroscopy and Scanning Electron Microscope, the immersion immune effect against S. agalactiae and S. iniae infection was evaluated. The results showed that compared with the control group, BNC-rSS significantly enhanced serum antibody production, related enzyme activities and immune-related genes expression. It was noteworthy that BNC-rSS vaccine improved immune protection of tilapia, with survival rates of 66.67 % (S. agalactiae) and 60.00 % (S. iniae), respectively, compared with those of rSS vaccine (30 % and 33.33 %, respectively). Our study indicated that the BNC-rSS nanovaccine could elicit robust immune responses in tilapia by immersion immunization, and had the potential to offer cross-protection against S. agalactiae and S. iniae infection in tilapia.

Oral delivery of a Streptococcus agalactiae vaccine to Nile tilapia (Oreochromis niloticus) using a novel cationic-based nanoemulsion containing bile salts.

Streptococcus agalactiae is one of Thailand's most important pathogens in tilapia aquaculture. Vaccination is a very effective method for protecting fish against disease in aquaculture. Oral vaccination is an interesting route for vaccine delivery as it mimics the pathogenesis of S. agalactiae and provides convenient administration for mass vaccination of fish. Moreover, gut mucosal immunity is associated with a mucus layer on the gastrointestinal tract. Therefore, this study aimed to develop a novel cationic-based nanoemulsion vaccine containing bile salts (NEB) coated by chitosan (CS) and determined its physicochemical characterization, morphology, in vitro mucoadhesive property, permeability, and acid-base tolerance. In addition, the efficacy of NEB-CS as an oral vaccination for Nile tilapia was evaluated in order to investigate the innate immune response and protection against S. agalactiae. The groups of fish consisted of: (1) deionized water as a non-vaccinated control (Control); (2) an inactivated vaccine formulated from formalin-killed bacteria (IB); and (3) a novel cationic-based nanoemulsion vaccine containing bile salts (NEB) coated by chitosan (CS). The control, IB, and NEB-CS were incorporated into commercial feed pellets and fed to Nile tilapia. In addition, we evaluated the serum bactericidal activity (SBA) for 14 days post-vaccination (dpv) and protective efficacy for 10 days post-challenge, respectively. The mucoadhesiveness, permeability, and absorption within the tilapia intestine were also assessed in vivo. The NEB-CS vaccine appeared spherical, with the nanoparticles having a size of 454.37 nm and a positive charge (+47.6 mV). The NEB-CS vaccine had higher levels of mucoadhesiveness and permeability than the NEB (p < 0.05). The relative percent survival (RPS) of IB and NEB-CS, when administered orally to fish, was 48% and 96%, respectively. Enhanced SBA was noted in the NEB-CS and IB vaccine groups compared to the control group. The results demonstrate that a feed-based NEB-CS can improve the mucoadhesiveness, permeability, and protective efficacy of the vaccine, and appear to be a promising approach to protecting tilapia in aquaculture against streptococcosis.