Immune response induced by a Streptococcus suis multi-serotype autogenous vaccine used in sows to protect post-weaned piglets.

Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no current commercial vaccines, the use of autogenous vaccines applied to gilts/sows to enhance transfer of passive immunity is an attractive alternative to protect weaned piglets. However, there is no universal standardization in the production of autogenous vaccines and the vaccine formulation may be highly different among licenced manufacturing laboratories. In the present study, an autogenous vaccine that included S. suis serotypes 2, 1/2, 5, 7 and 14 was prepared by a licensed laboratory and administrated to gilts using a three-dose program prior to farrowing. The antibody response in gilts as well as the passive transfer of antibodies to piglets was then evaluated. In divergence with previously published data with an autogenous vaccine produced by a different company, the increased response seen in gilts was sufficient to improve maternal antibody transfer to piglets up to 5 weeks of age. However, piglets would still remain susceptible to S. suis disease which often appears during the second part of the nursery period. Vaccination did not affect the shedding of S. suis (as well as that of the specific S. suis serotypes included in the vaccine) by either gilts or piglets. Although all antibiotic treatments were absent during the trial, the clinical protective effect of the vaccination program with the autogenous vaccine could not be evaluated, since limited S. suis cases were present during the trial, confirming the need for a complete evaluation of the clinical protection that must include laboratory confirmation of the aetiological agent involved in the presence of S. suis-associated clinical signs. Further studies to evaluate the usefulness of gilt/sow vaccination with autogenous vaccines to protect nursery piglets should be done.

Metagenomic next-generation sequencing confirmed a case of sporadic human infection with Streptococcus suis in an urban area.

INTRODUCTION: Streptococcus suis (S. suis) disease is a zoonotic infection caused by invasive S. suis and can lead to meningitis, septic shock, arthritis, and endocarditis. Early treatment is the key to reducing mortality. However, clinical manifestations of most cases are atypical, severely limiting rapid diagnosis and treatment. CASE REPORT: Here, we report a 74-year-old female patient diagnosed with S. suis infection. The main symptoms were hearing loss, lumbago, and scattered ecchymosis of the lower extremities and trunk. Blood non-specific infection indexes were significantly increased and platelets were significantly decreased; however, no pathogens were obtained from routine blood culture. Finally, the S. suis infection was confirmed by metagenomic next-generation sequencing (mNGS) of blood and cerebrospinal fluid. After antibiotic treatment, the limb and trunk scattered ecchymosis and lumbago symptoms were significantly relieved, but the hearing did not recover. CONCLUSIONS: Human infection with S. suis is rare in central cities, and it is easy to misdiagnose, especially in cases with atypical early symptoms. mNGS technology, combined with clinical observation, is helpful to clarify the direction of diagnosis and treatment, which is conducive to patient recovery.

Toxic Shock Syndrome (TSS) Caused by Group A Streptococcus: Novel Insights Within the Context of a Familiar Clinical Syndrome.

The emergence of invasive infections attributed to group A Streptococcus (GAS) infections, has resurged since the 1980s. The recent surge in reports of toxic shock syndrome due to GAS in Japan in 2024, while sensationalized in the media, does not represent a novel infectious disease per se, as its diagnosis, treatment, and prevention are already well-established. However, due to signs of increasing incidence since 2011, further research is needed. Health authorities in neighboring countries like The Republic of Korea should not only issue travel advisories but also establish meticulous surveillance systems and initiate epidemiological studies on the genotypic variations of this disease while awaiting various epidemiological research findings from Japan.

Machine Learning for Clinical Decision Support of Acute Streptococcal Pharyngitis: A Pilot Study.

BACKGROUND: Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance. OBJECTIVES: To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children. METHODS: We assessed 54 children aged 2-17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification. RESULTS: The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36). CONCLUSIONS: Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.

Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes.

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.

Development of novel Streptococcus equi vaccines with an assessment of their immunizing potentials and protective efficacies.

Strangles is a highly contagious disease of the equine upper respiratory tract caused by Streptococcus equi subspecies. Streptococcus equi subsp. equi (S. equi) and Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) was isolated, as local, hot, and field strains, from horses clinically suffering from respiratory distress. The isolated Streptococci were identified using bacteriological and molecular techniques. Four formulations of inactivated S. equi vaccines were developed and evaluated. The first formulation was prepared using the S. equi isolates, adjuvanted with MONTANIDE GEL adjuvant, while the second formulation was adjuvanted with MONTANIDE ISA-70 adjuvant. The other 2 formulations were inactivated combined vaccines prepared from both S. equi and S. zooepidemicus isolates. The 3rd formulation was the combined isolates adjuvanted with MONTANIDE GEL while the 4th formulation was the combined isolates adjuvanted with MONTANIDE ISA-70. The developed vaccines' physical properties, purity, sterility, safety, and potency were ensured. The immunizing efficacy was determined in isogenic BALB/c mice and white New Zealand rabbits using the passive hemagglutination test. Also, the antibodies' titer of the combined S. equi and S. zooepidemicus vaccine adjuvanted with MONTANIDE ISA-70 in foals was tracked using an indirect enzyme-linked immunosorbent assay. The protective efficacy of the developed vaccines was determined using a challenge test in both laboratory and field animal models, where a 75% protection rate was achieved. The combined vaccine proved to be more efficacious than the monovalent vaccine. Also, the MONTANIDE ISA-70 adjuvant provided significant protective efficacy than the MONTANIDE GEL. The current work is introducing a very promising mitigative and strategic controlling solution for strangles.

Genomic insights into the diversity, virulence, and antimicrobial resistance of group B Streptococcus clinical isolates from Saudi Arabia.

Introduction: Detailed assessment of the population structure of group B Streptococcus (GBS) among adults is still lacking in Saudi Arabia. Here we characterized a representative collection of isolates from colonized and infected adults. Methods: GBS isolates (n=89) were sequenced by Illumina and screened for virulence and antimicrobial resistance determinants. Genetic diversity was assessed by single nucleotide polymorphisms and core-genome MLST analyses. Results: Genome sequences revealed 28 sequence types (STs) and nine distinct serotypes, including uncommon serotypes VII and VIII. Majority of these STs (n=76) belonged to the human-associated clonal complexes (CCs) CC1 (33.71%), CC19 (25.84%), CC17 (11.24%), CC10/CC12 (7.87%), and CC452 (6.74%). Major CCs exhibited intra-lineage serotype diversity, except for the hypervirulent CC17, which exclusively expressed serotype III. Virulence profiling revealed that nearly all isolates (94.38%) carried at least one of the four alpha family protein genes (i.e., alphaC, alp1, alp2/3, and rib), and 92.13% expressed one of the two serine-rich repeat surface proteins Srr1 or Srr2. In addition, most isolates harbored the pilus island (PI)-2a alone (15.73%) or in combination with PI-1 (62.92%), and those carrying PI-2b alone (10.11%) belonged to CC17. Phylogenetic analysis grouped the sequenced isolates according to CCs and further subdivided them along with their serotypes. Overall, isolates across all CC1 phylogenetic clusters expressed Srr1 and carried the PI-1 and PI-2a loci, but differed in genes encoding the alpha-like proteins. CC19 clusters were dominated by the III/rib/srr1/PI-1+PI-2a (43.48%, 10/23) and V/alp1/srr1/PI-1+PI-2a (34.78%, 8/23) lineages, whereas most CC17 isolates (90%, 9/10) had the same III/rib/srr2/P1-2b genetic background. Interestingly, genes encoding the CC17-specific adhesins HvgA and Srr2 were detected in phylogenetically distant isolates belonging to ST1212, suggesting that other highly virulent strains might be circulating within the species. Resistance to macrolides and/or lincosamides across all major CCs (n=48) was associated with the acquisition of erm(B) (62.5%, 30/48), erm(A) (27.1%, 13/48), lsa(C) (8.3%, 4/48), and mef(A) (2.1%, 1/48) genes, whereas resistance to tetracycline was mainly mediated by presence of tet(M) (64.18%, 43/67) and tet(O) (20.9%, 14/67) alone or in combination (13.43%, 9/67). Discussion: These findings underscore the necessity for more rigorous characterization of GBS isolates causing infections.

Molecular profile and epidemiological traits of Streptococcus suis isolated from diseased pigs in western Canada reveal multiple-serotype infection: Implications for disease control.

Objective: Streptococcus suis is a major agent of disease in modern swine operations, linked to increased mortality, treatment costs, and secondary infections. Although it is ubiquitous in swine, only a fraction of pigs develop clinical disease. The goals of this study were to profile isolates obtained from diseased pigs in western Canada and to investigate potential associations with disease severity. Procedure: Isolates of S. suis (n = 128) from 75 diagnostic submission and 63 premises were paired with epidemiological surveys completed by submitting practitioners (n = 22). Whole-genome sequencing was used to type isolates. Results: The most prevalent serotypes identified were 1/2 (7.8%, 10/128), 2 (9.3%, 12/128), 3 (9.3%, 12/128), and 7 (7.8%, 10/128); and sequence types 28 (17%, 23/128) and 839 (14%, 19/128). There was no association between serotype or sequence type and organ source or barn location. Approximately 74% (14/19) of the premises had diseased animals colonized by > 1 S. suis serotype, but only 1 pig was simultaneously infected with multiple serotypes and sequence types. Serotype distribution from diseased pigs in western Canada differed from that of those in other geographic regions. Conclusion: Infection of diseased pigs by multiple serotypes should be considered when disease control strategies are implemented. No association between S. suis type and isolation organ was identified.

Le profil moléculaire et les caractéristiques épidémiologiques de Streptococcus suis isolés de porcs malades dans l'ouest du Canada révèlent une infection à sérotypes multiples : implications pour la maitrise de la maladie. Objectif: Streptococcus suis est un agent pathogène majeur dans les exploitations porcines modernes, lié à une mortalité accrue, aux coûts de traitement et aux infections secondaires. Bien qu'elle soit omniprésente chez le porc, seule une fraction des porcs développe une maladie clinique. Les objectifs de cette étude étaient de dresser le profil des isolats obtenus à partir de porcs malades dans l'ouest du Canada et d'étudier les associations potentielles avec la gravité de la maladie. Procédure: Des isolats de S. suis (n = 128) provenant de 75 soumissions pour diagnostic et de 63 sites ont été associés à des enquêtes épidémiologiques réalisées auprès des praticiens soumettant les échantillons (n = 22). Le séquençage du génome entier a été utilisé pour typer les isolats. Résultats: Les sérotypes les plus répandus identifiés étaient 1/2 (7,8 %, 10/128), 2 (9,3 %, 12/128), 3 (9,3 %, 12/128) et 7 (7,8 %, 10/128); et les types de séquence 28 (17 %, 23/128) et 839 (14 %, 19/128). Il n'y avait aucune association entre le sérotype ou le type de séquence et la source d'organes ou l'emplacement de la ferme. Environ 74 % (14/19) des exploitations abritaient des animaux malades colonisés par > 1 sérotype de S. suis, mais 1 seul porc était infecté simultanément par plusieurs sérotypes et types de séquences. La répartition des sérotypes chez les porcs malades de l'ouest du Canada différait de celle des porcs d'autres régions géographiques. Conclusion: L'infection des porcs malades par plusieurs sérotypes doit être envisagée lors de la mise en oeuvre de stratégies de maitrise de la maladie. Aucune association entre le type de S. suis et l'organe d'isolement n'a été identifiée.(Traduit par Dr Serge Messier).

Eliminate all risks: A call to reexamine the link between canine scabies and rheumatic heart disease.

Rheumatic heart disease (RHD) and acute rheumatic fever (ARF) disproportionately affect individuals in low-resource settings. ARF is attributed to an immune response to Group A Streptococcus (GAS) following GAS pharyngitis and potentially GAS impetigo in which infection can be initiated by scabies infestation. The burden of ARF and RHD in Aboriginal and Torres Strait Islander people in Australia is among the highest globally. Following recent calls to include dog management programs in ARF and RHD prevention programs, we believe it is timely to assess the evidence for this, particularly since previous recommendations excluded resources to prevent zoonotic canine scabies. While phylogenetic analyses have suggested that the Sarcoptes mite is host specific, they have differed in interpretation of the strength of their findings regarding species cross-over and the need for canine scabies control to prevent human itch. Given that there is also indication from case reports that canine scabies leads to human itch, we propose that further investigation of the potential burden of zoonotic canine scabies and intervention trials of canine scabies prevention on the incidence of impetigo are warranted. Considering the devastating impacts of ARF and RHD, evidence is required to support policy to eliminate all risk factors.

Establishment and application of a rapid visual diagnostic method for Streptococcus agalactiae based on recombinase polymerase amplification and lateral flow strips.

This study aims to establish a rapid diagnostic method for Streptococcus agalactiae (GBS) based on recombinase polymerase amplification (RPA) and lateral flow strips (LFS). The best primer pairs designed by SIP gene were screened according to the basic RPA reaction, then the probe was designed. The reaction condition was optimized based on the color development of the LFS detection line. To ascertain the reaction specificity, 10 common clinical pathogens and 10 clinical specimens of GBS were tested. Furthermore, the reaction sensitivity was assessed by utilizing a tenfold gradient dilution of GBS genomic DNA as templates. RPA-LFS method was compared to the qPCR assay and biochemical culture method for the Kappa consistency test. The RPA-LFS technique was able to complete the amplification process within 30 min and the results were observed on lateral flow strips. The method is highly sensitive, with a minimum detection limit of 1.31 ng for GBS. The RPA-LFS method showed consistent accuracy of results compared to qPCR and the culture-biochemical method. The establishment of this method is conducive to the development of on-site immediate detection, which can provide information for the timely development of a reasonable antimicrobial treatment plan, and has a greater potential for clinical application.

Chlorella vulgaris algae ameliorates chlorpyrifos toxicity in Nile tilapia with special reference to antioxidant enzymes and Streptococcus agalactiae infection.

BACKGROUND: Chlorpyrifos (CPF) is a widely used pesticide in the production of plant crops. Despite rapid CPF biodegradation, fish were exposed to wastewater containing detectable residues. Recently, medicinal plants and algae were intensively used in aquaculture to replace antibiotics and ameliorate stress impacts. METHODS AND RESULTS: An indoor experiment was conducted to evaluate the deleterious impacts of CPF pollution on Nile tilapia health and the potential mitigation role of Chlorella vulgaris algae. Firstly, the median lethal concentration LC50 - 72 h of CPF was determined to be 85.8 µg /L in Nile tilapia (35.6 ± 0.5 g body weight) at a water temperature of 27.5 °C. Secondly, fish were exposed to 10% of LC50 - 72 h for six weeks, and tissue samples were collected and examined every two weeks. Also, Nile tilapia were experimentally infected with Streptococcus agalactiae. Exposed fish were immunosuppressed expressed with a decrease in gene expressions of interleukin (IL) 1ß, IL-10, and tumor necrosis factor (TNF)-α. Also, a decline was recorded in glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) gene expression in the head kidney tissue. A high mortality rate (MR) of 100% was recorded in fish exposed to CPF for six weeks and challenged with S. agalactiae. Fish that received dietary C. vulgaris could restore gene expression cytokines and antioxidants compared to the control. After six weeks of CPF exposure, fish suffered from anemia as red blood cell count (RBCs), hemoglobin (Hb), and packed cell volume (PCV) significantly declined along with downregulation of serum total protein (TP), globulin (GLO), and albumin (ALB). Liver enzymes were significantly upregulated in fish exposed to CPF pollution, alanine aminotransferase (ALT) (42.5, 53.3, and 61.7 IU/L) and aspartate aminotransferase (AST) (30.1, 31.2, and 22.8) after 2, 4, and 6 weeks, respectively. On S. agalactiae challenge, high MR was recorded in Nile tilapia exposed to CPF (G3) 60%, 60%, and 100% in week 2, week 4, and week 6, and C. vulgaris provided a relative protection level (RPL) of 0, 14.29, and 20%, respectively. CONCLUSIONS: It was concluded that CPF pollution induces immunosuppressed status, oxidative stress, and anemic signs in Nile tilapia. In contrast, C. vulgaris at a 50 g/kg fish feed dose could partially ameliorate such withdrawals, restoring normal physiological parameters.

Bacteriophage-derived endolysins as innovative antimicrobials against bovine mastitis-causing streptococci and staphylococci: a state-of-the-art review.

Bacteriophage-encoded endolysins, peptidoglycan hydrolases breaking down the Gram-positive bacterial cell wall, represent a groundbreaking class of novel antimicrobials to revolutionize the veterinary medicine field. Wild-type endolysins exhibit a modular structure, consisting of enzymatically active and cell wall-binding domains, that enable genetic engineering strategies for the creation of chimeric fusion proteins or so-called 'engineered endolysins'. This biotechnological approach has yielded variants with modified lytic spectrums, introducing new possibilities in antimicrobial development. However, the discovery of highly similar endolysins by different groups has occasionally resulted in the assignment of different names that complicate a straightforward comparison. The aim of this review was to perform a homology-based comparison of the wild-type and engineered endolysins that have been characterized in the context of bovine mastitis-causing streptococci and staphylococci, grouping homologous endolysins with ≥ 95.0% protein sequence similarity. Literature is explored by homologous groups for the wild-type endolysins, followed by a chronological examination of engineered endolysins according to their year of publication. This review concludes that the wild-type endolysins encountered persistent challenges in raw milk and in vivo settings, causing a notable shift in the field towards the engineering of endolysins. Lead candidates that display robust lytic activity are nowadays selected from screening assays that are performed under these challenging conditions, often utilizing advanced high-throughput protein engineering methods. Overall, these recent advancements suggest that endolysins will integrate into the antibiotic arsenal over the next decade, thereby innovating antimicrobial treatment against bovine mastitis-causing streptococci and staphylococci.

Increase in invasive group A streptococcal infections (iGAS) in children and older adults, Norway, 2022 to 2024.

At the end of 2022 and most notably during the first half of 2023, the number of invasive group A streptococcus (iGAS) notifications increased in Norway, largely affecting children younger than 10 years, as observed in several other countries. Following this atypical season, a new surge in the number of iGAS notifications began in December 2023 and peaked between January and February 2024, now particularly affecting both children younger than 10 years and older adults (70 years and above).

An optimized caries model of Streptococcus mutans in rats and its application for evaluating prophylactic vaccines.

Dental caries is a prevalent oral disease that mainly results from Streptococcus mutans. Susceptibility to S. mutans decreased rapidly after weaning in a well-known rat model. However, owing to the lack of time to establish protective immunity ahead of challenge, the weaning rat model is suboptimal for assessing prophylactic vaccines against S. mutans infection. In this study, we found that, in adult rats, S. mutans cultured under air-restricted conditions showed dramatically increased colonization efficacy and accelerated development of dental caries compared with those cultured under air-unrestricted conditions. We propose that S. mutans cultured under air-restricted conditions can be used to develop an optimal caries model, especially for the evaluation of prophylactic efficacy against S. mutans. Therefore, we used the anti-caries vaccine, KFD2-rPAc, to reevaluate the protection against the challenge of S. mutans. In immunized rats, rPAc-specific protective antibodies were robustly elicited by KFD2-rPAc before the challenge. In addition to inhibiting the initial and long-term colonization of S. mutans in vivo, KFD2-rPAc immunization showed an 83% inhibitory efficacy against the development of caries, similar to that previously evaluated in a weaning rat model. These results demonstrate that culturing under air-restricted conditions can promote S. mutans infection in adult rats, thereby helping establish a rat infection model to evaluate the prophylactic efficacy of vaccines and anti-caries drugs.

Exploring the consent process among pregnant and breastfeeding women taking part in a maternal vaccine clinical trial in Kampala, Uganda: a qualitative study.

BACKGROUND: The involvement of pregnant women in vaccine clinical trials presents unique challenges for the informed consent process. We explored the expectations and experiences of the pregnant women, spouses/partners, health workers and stakeholders of the consent process during a Group B Streptococcus maternal vaccine trial. METHODS: We interviewed 56 participants including pregnant women taking part in the trial, women not in the trial, health workers handling the trial procedures, spouses, and community stakeholders. We conducted 13 in-depth interviews and focus group discussions with 23 women in the trial, in-depth interviews with 5 spouses, and 5 women not in the trial, key informant interviews with 5 health workers and 5 other stakeholders were undertaken. RESULTS: Decision-making by a pregnant woman to join a trial was done in consultation with spouse, parents, siblings, or trusted health workers. Written study information was appreciated by all but they suggested the use of audio and visual presentation to enhance understanding. Women stressed the need to ensure that their male partners received study information before their pregnant partners joined a clinical trial. Confidentiality in research was emphasised differently by individual participants; while some emphasised it for self, others were keen to protect their family members from being exposed, for allowing them to be involved in research. However, others wanted their community participation to be acknowledged. CONCLUSION: We found that pregnant women make decisions to join a clinical trial after consulting with close family. Our findings suggest the need for an information strategy which informs not only the pregnant woman, but also her family about the research she is invited to engage in.

Streptococcus suis serotype 4: a population with the potential pathogenicity in humans and pigs.

Streptococcus suis is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different S. suis serotypes exhibit diverse characteristics in population structure and pathogenicity. Surveillance data highlight the significance of S. suis serotype 4 (SS4) in swine streptococcusis, a pathotype causing human infections. However, except for a few epidemiologic studies, the information on SS4 remains limited. In this study, we investigated the population structure, pathogenicity, and antimicrobial characteristics of SS4 based on 126 isolates, including one from a patient with septicemia. We discovered significant diversities within this population, clustering into six minimum core genome (MCG) groups (1, 2, 3, 4, 7-2, and 7-3) and five lineages. Two main clonal complexes (CCs), CC17 and CC94, belong to MCG groups 1 and 3, respectively. Numerous important putative virulence-associated genes are present in these two MCG groups, and 35.00% (7/20) of pig isolates from CC17, CC94, and CC839 (also belonging to MCG group 3) were highly virulent (mortality rate ≥ 80%) in zebrafish and mice, similar to the human isolate ID36054. Cytotoxicity assays showed that the human and pig isolates of SS4 strains exhibit significant cytotoxicity to human cells. Antimicrobial susceptibility testing showed that 95.83% of strains isolated from our labs were classified as multidrug-resistant. Prophages were identified as the primary vehicle for antibiotic resistance genes. Our study demonstrates the public health threat posed by SS4, expanding the understanding of SS4 population structure and pathogenicity characteristics and providing valuable information for its surveillance and prevention.

Long-term healthcare utilisation, costs and quality of life after invasive group B Streptococcus disease: a cohort study in five low-income and middle-income countries.

INTRODUCTION: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa. METHODS: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data. RESULTS: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10). CONCLUSION: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention.

Identification of ClpB, a molecular chaperone involved in the stress tolerance and virulence of Streptococcus agalactiae.

Bacterial ClpB is an ATP-dependent disaggregate that belongs to the Hsp100/Clp family and facilitates bacterial survival under hostile environmental conditions. Streptococcus agalactiae, which is regarded as the major bacterial pathogen of farmed Nile tilapia (Oreochromis niloticus), is known to cause high mortality and large economic losses. Here, we report a ClpB homologue of S. agalactiae and explore its functionality. S. agalactiae with a clpB deletion mutant (∆clpB) exhibited defective tolerance against heat and acidic stress, without affecting growth or morphology under optimal conditions. Moreover, the ΔclpB mutant exhibited reduced intracellular survival in RAW264.7 cells, diminished adherence to the brain cells of tilapia, increased sensitivity to leukocytes from the head kidney of tilapia and whole blood killing, and reduced mortality and bacterial loads in a tilapia infection assay. Furthermore, the reduced virulence of the ∆clpB mutant was investigated by transcriptome analysis, which revealed that deletion of clpB altered the expression levels of multiple genes that contribute to the stress response as well as certain metabolic pathways. Collectively, our findings demonstrated that ClpB, a molecular chaperone, plays critical roles in heat and acid stress resistance and virulence in S. agalactiae. This finding provides an enhanced understanding of the functionality of this ClpB homologue in gram-positive bacteria and the survival strategy of S. agalactiae against immune clearance during infection.

Novel C-type lectin mediated non-specific cytotoxic cells killing activity through NCCRP-1 in nile tilapia (Oreochromis niloticus).

Non-specific cytotoxic cells (NCCs) are vital immune cells involved in teleost's non-specific immunity. As a receptor molecule on the NCCs' surface, the non-specific cytotoxic cell receptor protein 1 (NCCRP-1) is known to play a crucial role in mediating their activity. Nevertheless, there have been limited studies on the signal molecule that transmits signals via NCCRP-1. In this study, a yeast two-hybrid (Y2H) library of tilapia liver and head kidney was constructed and subsequently screened with the bait vector NCCRP-1 of Oreochromis niloticus (On-NCCRP-1) to obtain a C-type lectin (On-CTL) with an interacting protein sequence. Consequently, the full-length sequence of On-CTL was cloned and analyzed. The expression analysis revealed that On-CTL is highly expressed in the liver and is widely distributed in other tissues. Furthermore, On-CTL expression was significantly up-regulated in the brain, intestine, and head kidney following a challenge with Streptococcus agalactiae. A point-to-point Y2H method was also used to confirm the binding between On-NCCRP-1 and On-CTL. The recombinant On-CTL (rOn-CTL) protein was purified. In vitro experiments demonstrated that rOn-CTL can up-regulate the expression of killer effector molecules in NCCs via its interaction with On-NCCRP-1. Moreover, activation of NCCs by rOn-CTL resulted in a remarkable enhancement in their ability to eliminate fathead minnow cells, indicating that rOn-CTL effectively modulates the killing activity of NCCs through the NCC receptor molecule On-NCCRP-1. These findings significantly contribute to our comprehension of the regulatory mechanisms governing NCC activity, paving the way for future research in this field.

[Antibacterial therapy for acute streptococcal tonsillopharyngitis: results of a randomized comparative clinical trial with amoxicillin + clavulanic acid EXPRESS].

BACKGROUND: Acute tonsillopharyngitis is one of the most common types of respiratory tract infections. In case of bacterial etiologies of the disease, penicillin antibiotics are prescribed, in particular amoxicillin + clavulanic acid. Dispersible forms of antibiotics have a number of advantages over film-coated tablets and are characterized by better pharmacokinetic parameters that increase the effectiveness and safety of treatment, as well as patient compliance. AIM: To compare the effectiveness and safety of Amoxicillin + Clavulanic acid EXPRESS in the form of dispersible tablets and amoxicillin with clavulanic acid in film-coated tablets in the treatment of acute streptococcal tonsillopharyngitis. MATERIALS AND METHODS: A randomized comparative clinical study involved 60 adult patients diagnosed with acute streptococcal tonsillopharyngitis. Group 1 (n=30) received the Amoxicillin + Clavulanic acid EXPRESS, dispersible tablets, 875+125 mg 2 times a day at the beginning of meals. Group 2 (n=30) received Amoxiclav, film-coated tablets, 875+125 mg 2 times a day at the beginning of meals. The duration of the treatment was 10 days. The following procedures were performed to all participants: general clinical and otorhinolaryngological examinations, an express test to detect group A streptococcal antigens in a smear from the posterior pharyngeal wall (streptatest), assessment of symptoms of acute tonsillopharyngitis on the McIsaac scale, severity of sore throat, difficulty swallowing, swelling of the throat, measurement of body temperature, assessment of the clinical global impression of the therapy, adherence to treatment, frequency of the adverse reactions before treatment, 3 days after the beginning of therapy and after the course completion (day 10). RESULTS: Recovery occurred in 96.6% of patients in group 1 according to examination on the 10th day of treatment and in 93.3% of patients in group 2. The rate of fever regression was higher in group 1 - on the 3rd day of treatment, normalization of temperature was observed in 36.6% and 30% of patients in the comparison group. Pain syndrome, symptoms of throat swelling and difficulty swallowing significantly (p<0.01) regressed by the 10th day in patients of both treatment groups. The incidence of adverse reactions on the 10th day of treatment in group 1 was 10%, in group 2 - 33.3% (p=0.03). CONCLUSION: Amoxicillin + Clavulanic acid EXPRESS has high therapeutic efficacy in the treatment of acute streptococcal tonsillopharyngitis, comparable to the Amoxiclav in film-coated tablets. At the same time, dispersible tablets of Amoxicillin + Clavulanic acid EXPRESS demonstrated a significantly higher safety profile compared to the simple tablet form.