ABSTRACT
Newly synthesized vaccines prepared from formalin-killed bacteria Streptococcus pyogenes were investigated in the current study to evaluate the effectiveness of the newly synthesized vaccine as well as their safety by injected intraperitoneal. The study involved several steps 1st step is the preparation of the vaccine followed by the 2nd step: Evaluate the effectiveness and vaccine safety against pathogenic S. pyogenes through 4 different groups including control (Group I). Group II (Bacterial, infected group), Group III (Vaccine), and the Last group was the challenged group after the vaccination (Vacc + Bac). Different Immunological and biochemical parameters were measured in addition to hematological and histopathological examinations. For example, oxidative/antioxidants, inflammatory biomarkers, fragmentation and cell damage, and finally the histopathological study. The current study showed an increase in all oxidative, inflammatory, and cell damage (DNA fragmentation assays), additionally markedly elevation in histopathological cell damage in the infected group (Group II) compared with the control group. The vaccine and challenged after vaccination group (vaccine + Bacteria), showed great improvement in oxidative biomarkers (LPO) and an increase in antioxidants biomarkers (GSH, SOD, GST, DPPH, ABTS, GR and GPx), Also the inflammation and histopathological examination. The newly synthesized vaccine improved the resistance of Oreochromis niloticus and can be used as a preventive therapy agent for pathogenic bacteria S. pyogenes.
Subject(s)
Cichlids , Liver , Streptococcal Infections , Streptococcal Vaccines , Streptococcus pyogenes , Vaccination , Animals , Streptococcus pyogenes/immunology , Streptococcal Infections/prevention & control , Streptococcal Infections/immunology , Cichlids/immunology , Cichlids/microbiology , Liver/microbiology , Liver/pathology , Liver/metabolism , Vaccination/methods , Streptococcal Vaccines/immunology , Formaldehyde , Vaccines, Inactivated/immunology , Fish Diseases/prevention & control , Fish Diseases/microbiology , Fish Diseases/immunology , Antioxidants/pharmacology , Oxidative Stress/drug effects , BiomarkersABSTRACT
BACKGROUND: Maternal Group B Streptococcus (GBS) colonization is influenced by many factors but results are inconsistent. Consideration of antenatal risk factors may help inform decision making on GBS microbiological culture screening where universal screening is not standard of care. We sought to identify independent predictors of GBS colonization at 34-37 weeks gestation incorporating vaginal symptoms, perineal hygiene measures, sexual activity, and a potential novel factor, constipation. METHODS: In this prospective cross-sectional study, 573 women at 34-37 weeks gestation had an ano-vaginal swab taken and sent for selective culture for GBS. Women were asked about vaginal bleeding, discharge, irritation and candidiasis, antibiotic use during pregnancy, ano-vaginal hygiene practices such as douching and perineal cleansing after toileting, sexual intercourse related activities, and a potential novel factor for GBS carriage, constipation. Maternal basic demographics and obstetric-related characteristics were also collected. Bivariate analyses were performed to identify associates of GBS colonization. All variables with p < 0.05 found on bivariate analysis were then included into a model for multivariable binary logistic regression analysis to identify independent risk factors for GBS colonization. RESULTS: GBS colonization was found in 235/573 (41.0%) of participants. Twenty six independent variables were considered for bivariate analysis. Eight were found to have p < 0.05. Following adjusted analysis, six independent predictors of GBS colonization were identified: ethnicity, previous neonatal GBS prophylaxis, antenatal vaginal irritation, antibiotic use, recent panty liner use, and frequency of sexual intercourse. Vaginal discharge and perineal cleansing were not associated after adjustment. Recent douching and constipation were not associated on bivariate analysis. CONCLUSION: The identification of independent predictors of GBS colonization in late pregnancy may inform the woman and care provider in their shared decision making for microbiological screening at 35-38 weeks gestation in locations where universal GBS screening is not standard of care. ETHICS OVERSIGHT: This study was approved by the Medical Ethics Committee of University Malaya Medical Centre (UMMC) on August 9, 2022, reference number 2022328-11120.
Subject(s)
Constipation , Hygiene , Perineum , Pregnancy Complications, Infectious , Sexual Behavior , Streptococcal Infections , Streptococcus agalactiae , Vagina , Humans , Female , Pregnancy , Prospective Studies , Streptococcus agalactiae/isolation & purification , Adult , Constipation/microbiology , Constipation/prevention & control , Vagina/microbiology , Cross-Sectional Studies , Pregnancy Complications, Infectious/microbiology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/diagnosis , Streptococcal Infections/prevention & control , Streptococcal Infections/diagnosis , Perineum/microbiology , Perineum/injuries , Risk Factors , Anal Canal/microbiology , Pregnancy Trimester, ThirdABSTRACT
A maternal vaccine to protect newborns against invasive Streptococcus agalactiae infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy and induce strong immune responses and placental transfer of protective antibodies. Polysaccharide vaccines against S. agalactiae conjugated to protein carriers are in advanced stages of development. Additionally, protein-based vaccines are also in development, showing great promise as they can provide protection regardless of serotype. Furthermore, safety concerns regarding a new vaccine are the main barriers identified. Here, we present vaccines in development and identified safety, cost, and efficacy concerns, especially in high-need, low-income countries.
Subject(s)
Streptococcal Infections , Streptococcal Vaccines , Streptococcus agalactiae , Streptococcus agalactiae/immunology , Humans , Streptococcal Infections/immunology , Streptococcal Infections/prevention & control , Streptococcal Infections/microbiology , Streptococcal Vaccines/immunology , Pregnancy , Female , Animals , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/microbiology , Vaccine Development , Infant, Newborn , Antibodies, Bacterial/immunologyABSTRACT
Intraamniotic inflammation and infection complicate 2% to 5% of term deliveries. Group B Streptococcus (GBS) is a common cause of intraamniotic infection associated with invasive neonatal disease and maternal morbidity. Universal vaginal-rectal screening for GBS colonization is recommended between 36 and 37 weeks. Intrapartum antibiotic prophylaxis is recommended for individuals with positive GBS screens and other risk factors. Intravenous penicillin is the preferred antimicrobial agent. Individuals with penicillin allergies may receive cefazolin for low-risk allergies and either clindamycin or vancomycin for high-risk allergies, depending on their antimicrobial susceptibilities. Clinical trials are underway to evaluate the safety and immunogenicity of maternal anti-GBS vaccine candidates.
Subject(s)
Anti-Bacterial Agents , Antibiotic Prophylaxis , Chorioamnionitis , Pregnancy Complications, Infectious , Streptococcal Infections , Streptococcus agalactiae , Humans , Pregnancy , Streptococcal Infections/diagnosis , Streptococcal Infections/drug therapy , Streptococcal Infections/prevention & control , Female , Antibiotic Prophylaxis/methods , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/microbiology , Pregnancy Complications, Infectious/prevention & control , Anti-Bacterial Agents/therapeutic use , Chorioamnionitis/microbiology , Chorioamnionitis/drug therapy , Streptococcal Vaccines , Infant, NewbornABSTRACT
Group B Streptococcus (GBS) is the leading cause of bacterial neonatal sepsis. This study aimed to confirm the effect of Ligilactobacillus salivarius V4II-90 on GBS colonisation during pregnancy. A randomised, multicentre, double-blind, placebo-controlled, parallel-group study was conducted in seven hospitals in Madrid, Spain. The sample was broken down into two groups with 20 participants each (n = 40) in order to show reduced GBS colonisation frequency in the probiotic versus the placebo group. Pregnant participants positive for vaginal-rectal colonisation before or during the 13th week of gestation were randomly assigned to either the placebo or the probiotic group. The probiotic, L. salivarius V4II-90 at 1 × 109 cfu/day was administered for 12 weeks, starting at week 21-23 of gestation. The primary outcome was the percentage of participants with vaginal and/or rectal GBS colonisation at the end of the intervention period (35 weeks of gestation). Secondary outcomes were changes in the microbial composition of vaginal and rectal exudates; premature delivery; premature rupture of membranes; intrapartum antibiotics; new-borns with early or late-onset GBS sepsis; adverse events (AEs); and GBS test results performed at the hospital at week 35 of gestation. Of the 481 participants included, 44 were vaginal-rectal colonised with GBS and randomised. 43 completed the study (20 in the probiotic group and 23 in the placebo group). After intervention, GBS was eradicated in six participants (27%) from the placebo group and in twelve participants (63%) from the probiotic group ( P = 0.030). None of the 185 AEs reported were identified as possibly, probably, or definitely related to the investigational product. In conclusion, oral administration of L. salivarius V4II-90 is a safe and successful strategy to significantly decrease the rates of GBS colonisation at the end of pregnancy and, therefore, to reduce the exposure of subjects and their infants to intrapartum antibiotic prophylaxis. Trial registered at ClinicalTrials.gov: number NCT03669094.
Subject(s)
Ligilactobacillus salivarius , Pregnancy Complications, Infectious , Probiotics , Rectum , Streptococcal Infections , Streptococcus agalactiae , Vagina , Humans , Female , Pregnancy , Probiotics/administration & dosage , Double-Blind Method , Streptococcus agalactiae/growth & development , Streptococcus agalactiae/drug effects , Streptococcal Infections/prevention & control , Streptococcal Infections/microbiology , Streptococcal Infections/drug therapy , Adult , Vagina/microbiology , Rectum/microbiology , Ligilactobacillus salivarius/physiology , Pregnancy Complications, Infectious/microbiology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/drug therapy , Infant, Newborn , Spain , Young AdultABSTRACT
Tilapia is one of the most important farmed fish in the world and the most cultivated in Brazil. The increase of this farming favors the appearance of diseases, including bacterial diseases. Therefore, the aim of this study was to evaluate the bactericidal activity of copaiba oil, Copaifera duckei, against Streptococcus agalactiae and Flavobacterium columnare and the dietary effect of copaiba oil on zootechnical performance, hematological, biochemical, immunological, and histological analysis before and after an intraperitoneal infection (body cavity) with S. agalactiae in Nile tilapia. For this, fish were randomly distributed into 15 fiber tanks in five treatments (0, 0.25, 0.50, 0.75, and 1.0%) and fed with a commercial diet supplemented with copaiba oil for 30 days. After this period, the fish were randomly redistributed for the experimental challenge with S. agalactiae into six treatments (T0, T1, T2, T3, T4, and T5), the fish were anesthetized, and blood samples were collected to assess hematological, biochemical, immunological, and histological parameters. Copaiba oil showed bactericidal activity against Streptococcus spp. and Flavobacterium spp. in vitro. In addition, concentrations of 0.75 and 1.0% of copaiba oil have an anti-inflammatory effect and improve hematological and immunological parameters, increasing leukocyte numbers, albumin, and serum lytic activity. Furthermore, there is an increase in the intestinal villus length and tissue damage in groups at concentrations of 0.75 and 1.0% of copaiba oil. In conclusion, copaiba oil presented bactericidal activity against Streptococcus spp. and Flavobacterium spp. in vitro, and oral supplementation at concentrations of 0.75 and 1.0% compared to the control group enhanced non-specific immune parameters and digestibility in Nile Tilapia.
Subject(s)
Cichlids , Dietary Supplements , Fish Diseases , Flavobacterium , Streptococcus agalactiae , Animals , Streptococcus agalactiae/drug effects , Flavobacterium/drug effects , Fish Diseases/microbiology , Fish Diseases/drug therapy , Fish Diseases/prevention & control , Fabaceae/chemistry , Anti-Bacterial Agents/pharmacology , Streptococcal Infections/veterinary , Streptococcal Infections/drug therapy , Streptococcal Infections/prevention & control , Plant Oils/pharmacology , Flavobacteriaceae Infections/veterinary , Flavobacteriaceae Infections/microbiology , Flavobacteriaceae Infections/drug therapy , Flavobacteriaceae Infections/prevention & control , Animal Feed , Administration, Oral , Aquaculture/methodsABSTRACT
Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a predominant pathogen of neonatal sepsis, commonly associated with early-onset neonatal sepsis. GBS has also been associated with cases of late-onset sepsis potentially originating from the intestine. Previous findings have shown GBS can colonize the infant intestinal tract as part of the neonatal microbiota. To better understand GBS colonization dynamics in the neonatal intestine, we collected stool and milk samples from prematurely born neonates for identification of potential pathogens in the neonatal intestinal microbiota. GBS was present in approximately 10% of the cohort, and this colonization was not associated with maternal GBS status, delivery route, or gestational weight. Interestingly, we observed the relative abundance of GBS in the infant stool negatively correlated with maternal IgA concentration in matched maternal milk samples. Using a preclinical murine model of GBS infection, we report that both vertical transmission and direct oral introduction resulted in intestinal colonization of GBS; however, translocation beyond the intestine was limited. Finally, vaccination of dams prior to breeding induced strong immunoglobulin responses, including IgA responses, which were associated with reduced mortality and GBS intestinal colonization. Taken together, we show that maternal IgA may contribute to infant immunity by limiting the colonization of GBS in the intestine.
Subject(s)
Bacterial Translocation , Immunoglobulin A , Streptococcal Infections , Streptococcus agalactiae , Streptococcus agalactiae/growth & development , Streptococcus agalactiae/immunology , Animals , Streptococcal Infections/microbiology , Streptococcal Infections/prevention & control , Streptococcal Infections/immunology , Female , Infant, Newborn , Humans , Mice , Infectious Disease Transmission, Vertical , Feces/microbiology , Intestines/microbiology , Intestines/immunology , Milk, Human/microbiology , Gastrointestinal Microbiome , Pregnancy , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Disease Models, Animal , Mice, Inbred C57BL , MaleABSTRACT
Group B Streptococcus (GBS) disease in neonates occurs in two forms: early-onset disease (EOD), (day 0-6), and late-onset disease (LOD), (day 7-90). This review investigates that risk-based intrapartum screening and antibiotics have reduced the incidence of EOD, but not LOD, in Denmark. No clinical or laboratory tests can rule out GBS disease at symptom onset. Thus, a high proportion of uninfected infants receive antibiotics, although this varies widely, and may be reduced by strategies of antibiotic stewardship. A future GBS vaccine for pregnant women may potentially reduce disease burden and antibiotic exposure.
Subject(s)
Anti-Bacterial Agents , Streptococcal Infections , Streptococcus agalactiae , Humans , Streptococcal Infections/diagnosis , Streptococcal Infections/prevention & control , Streptococcal Infections/drug therapy , Infant, Newborn , Streptococcus agalactiae/isolation & purification , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Female , Pregnancy , Denmark/epidemiology , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/microbiology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/drug therapy , Infant , Streptococcal Vaccines/administration & dosage , Infectious Disease Transmission, Vertical/prevention & controlABSTRACT
Streptococcus suis is a bacterial pathogen that can cause significant economic losses in the swine industry due to high morbidity and mortality rates in infected animals. Vaccination with bacterins, which consist of inactivated bacteria and adjuvants to enhance the pig's immune response, is an effective approach to control S. suis infections in piglets. Here we provide a description of S. suis bacterins and the methods for vaccine preparation. Moreover, this chapter also describes the addition of recombinant Sao (rSao-L) protein to the S. suis bacterin, aiming to enhance the efficacy of the bacterins against S. suis in piglets. Furthermore, the methods for evaluating the immune response elicited by the bacterins are also covered in this chapter.
Subject(s)
Streptococcus suis , Animals , Swine , Streptococcus suis/immunology , Streptococcal Infections/immunology , Streptococcal Infections/microbiology , Streptococcal Infections/prevention & control , Streptococcal Infections/veterinary , Swine Diseases/microbiology , Swine Diseases/prevention & control , Swine Diseases/immunology , Vaccination/methods , Bacterial Vaccines/immunology , Adjuvants, Immunologic/pharmacology , Antibodies, Bacterial/immunology , Recombinant Proteins/immunology , Recombinant Proteins/genetics , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosageABSTRACT
Group B Streptococcus (GBS) is a frequent colonizer of the human genital and gastrointestinal tract. In pregnant or postpartum persons, colonization is often asymptomatic and can contribute to infectious morbidity in both the parturient and the newborn. The prevalence of invasive GBS disease has dramatically decreased over the past 3 decades. However, despite standardized clinical algorithms, GBS disease remains a public health concern. Our review summarizes the GBS bacteria pathophysiology, morbidity, management guidelines, and summarizes ongoing research. While novel testing and parturient vaccination are being explored, barriers exist, preventing guideline updates and widespread implementation.
Subject(s)
Pregnancy Complications, Infectious , Streptococcal Infections , Streptococcus agalactiae , Humans , Female , Streptococcal Infections/prevention & control , Streptococcal Infections/diagnosis , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/microbiology , Infectious Disease Transmission, Vertical/prevention & control , Infant, Newborn , Streptococcal Vaccines , Anti-Bacterial Agents/therapeutic useABSTRACT
Streptococcus suis is one of the major pathogens of pigs circulating worldwide, and the development of vaccines will help to effectively control streptococcosis in swine. In this study, we evaluated the potential of three membrane associated proteins, histidine kinase (HK), glycosyltransferase family 2 (Gtf-2) and phosphate binding protein (PsbP) of S. suis as subunit vaccines. Bioinformatics analysis shows that protein ABC is highly conserved in S. suis. To verify the protective effects of these proteins in animal models, recombinant protein HK, Gtf-2 and PsbP were used to immunize BALB/c mice separately. The results showed that these proteins immunization in mice can effectively induce strong humoral immune responses, protect mice from cytokine storms caused by S. suis infection, and have a significant protective effect against lethal doses of S. suis infection. Furthermore, antibodies with opsonic activity exist in the recombinant proteins antiserum to assist phagocytic cells in killing S. suis. Overall, these results indicated that these recombinant proteins all elicit good immune protective effect against S. suis infection and can be represent promising candidate antigens for subunit vaccines against S. suis.
Subject(s)
Antibodies, Bacterial , Bacterial Proteins , Disease Models, Animal , Mice, Inbred BALB C , Recombinant Proteins , Streptococcal Infections , Streptococcal Vaccines , Streptococcus suis , Vaccines, Subunit , Streptococcus suis/immunology , Streptococcus suis/genetics , Animals , Streptococcal Infections/prevention & control , Streptococcal Infections/immunology , Streptococcal Infections/microbiology , Mice , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Vaccines, Subunit/immunology , Vaccines, Subunit/genetics , Recombinant Proteins/immunology , Recombinant Proteins/genetics , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosage , Streptococcal Vaccines/genetics , Serogroup , Cytokines/metabolism , Female , Membrane Proteins/immunology , Membrane Proteins/genetics , Immunity, Humoral , Antigens, Bacterial/immunology , Antigens, Bacterial/genetics , Swine Diseases/prevention & control , Swine Diseases/immunology , Swine Diseases/microbiology , Swine , Computational BiologyABSTRACT
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.
Subject(s)
Horse Diseases , Mice, Inbred BALB C , Streptococcal Infections , Streptococcal Vaccines , Streptococcus equi , Streptococcus , Animals , Streptococcus equi/immunology , Horses , Rabbits , Streptococcal Infections/veterinary , Streptococcal Infections/prevention & control , Streptococcal Infections/microbiology , Streptococcal Infections/immunology , Mice , Horse Diseases/prevention & control , Horse Diseases/microbiology , Horse Diseases/immunology , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosage , Female , Antibodies, Bacterial/blood , Adjuvants, Immunologic/administration & dosage , Vaccines, Inactivated/immunologyABSTRACT
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.
Subject(s)
Autovaccines , Streptococcal Infections , Streptococcus suis , Swine Diseases , Animals , Streptococcus suis/immunology , Swine , Swine Diseases/prevention & control , Swine Diseases/microbiology , Swine Diseases/immunology , Streptococcal Infections/veterinary , Streptococcal Infections/prevention & control , Streptococcal Infections/immunology , Female , Immunity, Maternally-Acquired , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosage , Serogroup , Vaccination/veterinaryABSTRACT
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.
Subject(s)
Breast Feeding , Decision Making , Informed Consent , Pregnant Women , Qualitative Research , Humans , Female , Pregnancy , Uganda , Informed Consent/ethics , Adult , Pregnant Women/psychology , Male , Spouses , Focus Groups , Clinical Trials as Topic/ethics , Streptococcal Infections/prevention & control , Confidentiality , Research Subjects/psychology , Young Adult , Health Personnel/psychology , Streptococcus agalactiaeABSTRACT
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.
Subject(s)
Antibodies, Bacterial , Dental Caries , Disease Models, Animal , Streptococcus mutans , Animals , Dental Caries/prevention & control , Dental Caries/microbiology , Dental Caries/immunology , Streptococcus mutans/immunology , Rats , Antibodies, Bacterial/immunology , Antibodies, Bacterial/blood , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosage , Streptococcal Infections/prevention & control , Streptococcal Infections/immunology , Streptococcal Infections/microbiology , Female , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. METHODS: We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. RESULTS: Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively." CONCLUSIONS: The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.
Subject(s)
Streptococcal Infections , Streptococcal Vaccines , Streptococcus agalactiae , Virulence Factors , Whole Genome Sequencing , Humans , Streptococcus agalactiae/genetics , Streptococcus agalactiae/pathogenicity , Streptococcus agalactiae/drug effects , Streptococcus agalactiae/immunology , Streptococcus agalactiae/isolation & purification , Streptococcus agalactiae/classification , Whole Genome Sequencing/methods , Virulence Factors/genetics , Infant , Streptococcal Infections/microbiology , Streptococcal Infections/epidemiology , Streptococcal Infections/prevention & control , Streptococcal Vaccines/immunology , Infant, Newborn , China/epidemiology , Female , Serogroup , Male , Drug Resistance, Bacterial/genetics , Genome, Bacterial , Anti-Bacterial Agents/pharmacologyABSTRACT
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.
Subject(s)
Dog Diseases , Rheumatic Heart Disease , Scabies , Animals , Scabies/veterinary , Scabies/prevention & control , Scabies/epidemiology , Dogs , Humans , Dog Diseases/prevention & control , Dog Diseases/parasitology , Dog Diseases/epidemiology , Rheumatic Heart Disease/prevention & control , Rheumatic Heart Disease/epidemiology , Australia/epidemiology , Zoonoses/prevention & control , Impetigo/microbiology , Impetigo/prevention & control , Streptococcus pyogenes , Streptococcal Infections/veterinary , Streptococcal Infections/prevention & control , Streptococcal Infections/epidemiology , Streptococcal Infections/microbiology , Risk Factors , Rheumatic Fever/prevention & controlABSTRACT
In response to the global threat posed by bacterial pathogens, which are the second leading cause of death worldwide, vaccine development is challenged by the diversity of bacterial serotypes and the lack of immunoprotection across serotypes. To address this, we introduce BacScan, a novel genome-wide technology for the rapid discovery of conserved highly immunogenic proteins (HIPs) across serotypes. Using bacterial-specific serum, BacScan combines phage display, immunoprecipitation, and next-generation sequencing to comprehensively identify all the HIPs in a single assay, thereby paving the way for the development of universally protective vaccines. Our validation of this technique with Streptococcus suis, a major pathogenic threat, led to the identification of 19 HIPs, eight of which conferred 20-100% protection against S. suis challenge in animal models. Remarkably, HIP 8455 induced complete immunity, making it an exemplary vaccine target. BacScan's adaptability to any bacterial pathogen positions it as a revolutionary tool that can expedite the development of vaccines with broad efficacy, thus playing a critical role in curbing bacterial transmission and slowing the march of antimicrobial resistance.
Subject(s)
Bacterial Proteins , Animals , Mice , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Streptococcal Infections/immunology , Streptococcal Infections/prevention & control , Streptococcus suis/immunology , Streptococcus suis/genetics , Genome, Bacterial , High-Throughput Nucleotide Sequencing , Female , Antigens, Bacterial/immunology , Antigens, Bacterial/genetics , Humans , Bacterial Vaccines/immunologyABSTRACT
Streptococcosis outbreaks caused by Streptococcus agalactiae infection in tilapia aquaculture have been consistently reported and associated with high mortality and morbidity leading to significant economic losses. Existing vaccine candidates against Streptococcus spp. are designed for intraperitoneal injections that are not practical and labor-intensive which have prompted farmers to protect aquatic animals with antibiotics, thus encouraging the emergence of multidrug resistant bacteria. In this study, a live recombinant L. lactis vaccine expressing a 1403 bp surface immunogenic protein (SIP) and a 1100 bp truncated SIP (tSIP) gene was developed and evaluated against S. agalactiae infection in tilapia. Both SIP and tSIP sequences were cloned and transformed into L. lactis. The recombinant L.lactis vaccine was orally administered to juvenile tilapia for a month. Detection of SIP-specific serum IgM in vaccinated groups compared to control groups indicated that recombinant proteins expressed from L. lactis could elicit immunogenic reactions in tilapia. Fish immunized with the tSIP vaccine also showed the highest level of protection compared to other test groups, and the mortality rate was significantly reduced compared to both control groups. The relative percentage of survival (RPS) against S. agalactiae for both SIP and tSIP-vaccinated groups was 50 % and 89 %, respectively, at 14 days post-challenge. Significant up-regulation of IgM, IL-1ß, IL-10, TNF-α and IFN-γ were observed at day 34 between the vaccinated and control groups. These results indicated that the recombinant lactococcal tSIP vaccine can elicit both cell-mediated and humoral responses and is recommended as a potential oral vaccine against S. agalactiae infection. Future work will include further in vivo challenge assessments of this vaccine candidate fused with adjuvants to boost immunogenicity levels in tilapia.
Subject(s)
Cichlids , Fish Diseases , Streptococcal Infections , Streptococcus agalactiae , Animals , Streptococcus agalactiae/immunology , Streptococcal Infections/veterinary , Streptococcal Infections/prevention & control , Streptococcal Infections/immunology , Fish Diseases/prevention & control , Fish Diseases/immunology , Cichlids/immunology , Administration, Oral , Vaccines, Synthetic/immunology , Vaccines, Synthetic/administration & dosage , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosage , Bacterial Vaccines/immunology , Bacterial Vaccines/administration & dosage , Lactococcus lactis/genetics , Lactococcus lactis/immunology , Bacterial Proteins/immunology , Bacterial Proteins/geneticsABSTRACT
Streptococcosis, an emerging infectious disease caused by Streptococcus agalactiae, has had adverse effects on farmed tilapia. Several vaccines have been developed to prevent this disease and induce a specific immune response against S. agalactiae infection. In this study the use of MONTANIDE™ GR01, a new adjuvant for oral vaccination, was optimized for use in tilapia under laboratory and field studies. In the laboratory trial the immune response and protective efficacy of two doses of MONTANIDE™ GR01, 20 % (w/w) and 2 % (w/w), included into the feed-based adjuvanted vaccines were assessed comparatively. Following immunization, the innate immune parameters studied in serum, including lysozyme, myeloperoxidase, catalase and glutathione peroxidase activity, were all increased significantly. Furthermore, specific IgM antibodies against S. agalactiae were induced significantly in serum post-vaccination, with higher levels observed in both groups that received the feed-based adjuvanted vaccine. Under both injection and immersion challenge conditions, the relative percent survival for the feed-based adjuvanted vaccine groups ranged from 78 % to 84 %. Following use of the low dose concentration of MONTANIDE™ GR01 for oral vaccination of tilapia in cage culture systems, several innate immune parameters were effectively enhanced in the immunized fish. Similarly, the levels of specific IgM antibodies in the serum of feed-based vaccinated fish were significantly enhanced, reaching their highest levels 2-5 months post-vaccination. Cytokines associated with innate and adaptive immunity were also examined, and the expression levels of several genes showed significant up-regulation. This indicates that both cellular and humoral immune responses were induced by the feed-based adjuvanted vaccine. The economic impact of a feed-based adjuvanted vaccine was examined following vaccination, considering the growth performance and feed utilization of the fish. It was found that the Economic Performance Index and Economic Conversion Ratio were unaffected by vaccination, further demonstrating that there are no negative impacts associated with administering a feed-based vaccine to fish. In conclusion, the data from this study indicate that MONTANIDE™ GR01 is a highly valuable adjuvant for oral vaccination, as demonstrated by its ability to induce a strong immune response and effectively prevent streptococcal disease in Nile tilapia.