Search Results (230)

Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack of studies on the prevalence of Streptococcus pneumoniae (S. pneumoniae) serotypes among vaccinated children. This research aimed to explore and compare the prevalence of nasopharyngeal pneumococcal carriage, serotype distribution, and antibiotic resistance patterns in healthy PCV13-vaccinated and -unvaccinated children. Methods: From August 2023 to November 2024, a multi-center, cross-sectional observational study was conducted in Tehran, Iran. This study included 204 nasopharyngeal samples collected from children aged from 18 to 59 months, involving both cases of children vaccinated with PCV13 and unvaccinated populations. S. pneumoniae was identified through a combination of culture methods and biochemical tests, confirmed by real-time PCR. Serotyping was achieved using cpsB sequencing, and the minimum inhibitory concentration method was employed to assess antibiotic resistance. Results: This study revealed similar S. pneumoniae carriage rates between PCV13-vaccinated and -unvaccinated Iranian children (20.6% vs. 21.6%). Serotypes 23F and 19F were prevalent in unvaccinated children, while 15B/15C was more prevalent in PCV13-vaccinated children. The included S. pneumoniae serotypes in PCV13 were detected more in the unvaccinated group. PCV13-vaccinated children exhibited no penicillin-resistant pneumococcal isolates, although four isolates were non-susceptible in unvaccinated children. Both groups showed substantial resistance to erythromycin and SXT. Previous respiratory infections, daycare attendance, residence in Tehran, and a history of antibiotic consumption increased the risk of pneumococcal carriage. Conclusions: PCV13 vaccination influences pneumococcal serotype distribution and antimicrobial susceptibility, although there was no significant difference regarding carriage rates between vaccinated and unvaccinated groups. These findings highlight the critical importance of vaccination in reducing invasive serotypes and antimicrobial resistance in children under five years old, emphasizing the importance of national PCV vaccination programs alongside continuous serotype surveillance. Full article

Maternal vaginal and rectal colonization by Streptococcus agalactiae (group B streptococcus, GBS) is the main risk factor for the development of newborn early-onset GBS disease (GBS-EOD). Much effort is in place for its prevention, including the development of vaccines. Currently, both a hexavalent glycoconjugate GBS vaccine against the most prevalent serotypes and a protein subunit vaccine have completed phase two clinical trials. GBS surveillance in both maternal carriage and neonatal disease is therefore important in establishing the coverage of the potential vaccines and in setting up the basis for pre- and post-marketing surveillance. A single-site study was conducted in the years 2020–2021 on the characteristics of 325 GBS strains (serotype distribution; identification of the alpha-like protein family member; and resistance to macrolides, tetracycline, and high-level gentamicin) isolated from the vaginal/rectal site in women in late pregnancy as well as in seven cases of GBS-EOD and one case of GBS-related stillbirth occurring in the same location and time period. The study indicated that the coverage of the developing vaccines was excellent (97.2% for the hexavalent glycoconjugate vaccine and 98.7% for the alpha-like protein subunit vaccine). However, the detection of the serotypes VI, VII, and IX—not covered by current vaccine formulations—accounting for 3.0% of isolates, as well as of negative alpha-like GBS strains from maternal carriage (1.2%), should be closely monitored over time. The high rates of GBS resistance to erythromycin (33.5%) and to clindamycin (29.5% in maternal carriage and 57.1% in GBS-EOD) was mostly due to the ever-increasing spread of the multidrug-resistant ST-17 subclone of serotype III. This finding, along with the newly emerging high-level gentamicin resistance in carriers (4.0%), mainly in serotype IV strains, poses a threat for the continued effectiveness of antibiotic therapy in invasive disease. Full article

Background/Objectives: Perineal obstetrical trauma sustained during vaginal delivery has a profound impact on female quality of life. The aim of the cross-sectional study was to analyze the association between active bacterial cervical infection and group B Streptococcus (GBS) rectovaginal colonization in the 35th–37th weeks of pregnancy with the degree of delivery perineal trauma. Methods: The study included 778 women after vaginal delivery. Maternal characteristics, including age, concomitant diseases, parity, obstetrical history, and cervical swab results conducted at admission and rectovaginal bacterial swabs at the 35th–37th weeks of pregnancy, were analyzed. The rates of perineal tears were compared between the physiological and pathological cervical swab groups and between the GBS-positive and GBS-negative colonization groups. Results: At admission to delivery, active cervical infection was diagnosed in 269 (35.9%) women. After vaginal delivery, 361 (49.3%) women had an intact perineum, and 288 (39.3%), 78 (10.7%), 4 (0.6%), and 1 (0.1%) had 1st–4th-degree perineal tears, respectively. Statistical analyses of the logistic regression model found that GBS colonization at the 35th–37th weeks of pregnancy (OR 1.56, p = 0.035) and pathological flora at admission (OR 1.54, p = 0.019) were associated with perineal tears. A higher vaginal parity was found to be a protective factor (OR 0.49, p < 0.000). Conclusions: High birthweight, longer second stage of labor duration, and primiparity were associated with increased rates of perineal trauma. Active cervical infection at admission and GBS colonization at the 35th–37th weeks of pregnancy were found to be risk factors for perineal tears. A protective factor for an intact perineum was a higher number of prior vaginal deliveries. Full article

Invasive neonatal GBS infections constitute a major cause of sepsis and meningitis in Western countries. Vaginal/rectal GBS colonization during pregnancy is the main risk factor for the development of early-onset infections (GBS-EOD) in newborn by vertical transmission at birth, in addition to prematurity and stillbirth. In Italy, intrapartum antibiotic prophylaxis (IAP) to prevent GBS-EOD is offered to pregnant women who tested as GBS-positive in late pregnancy. Passive surveillance in Italy showed that a non-negligible number of GBS-EOD cases (about 50%) occurred from GBS-negative pregnant women. This finding prompted the launch of a national online survey from 15 December 2022 to 12 February 2023 to investigate the microbiological procedures followed for GBS identification in Italian public and private microbiology laboratories, the prevalence of maternal GBS colonization, and the incidence of GBS-EOD cases. The survey results demonstrated that national guidelines for the prevention of EOD-GBS cases as well as harmonization of microbiological methodologies for GBS identification in the antenatal screening are needed. Full article

Background: Group A Streptococcus (GAS) is a major human pathogen associated with serious diseases. Evaluating immune responses against GAS vaccines—immunogenicity, quality, and efficacy—is complicated by interference from co-infections, like Staphylococcus aureus (S. aureus). We aimed to evaluate peptide-based GAS vaccines in mice for antisera efficacy against standard and mutant GAS strains and to assess immunological methods under co-infection conditions. Methods: Female C57BL/6 mice were infected with S. aureus and immunized with various M-protein-derived peptide antigens: J8, J8i, J8i-J8i, and the native p145 sequence. Two novel, conserved M-protein-derived antigens (NTD and CTD2) were also evaluated. Enzyme-linked immunosorbent assays (ELISAs) were used to assess immunogenicity and GAS-specific antibody responses. Peptide antigens were either conjugated to or physically mixed with the PADRE T-helper epitope and tested for enhanced antisera immunogenicity and opsonic efficacy. Result: ELISA against the immunizing peptides as coating antigens reflected the immunogenicity, while p145-based ELISA correlated with GAS-specific antibody titres without S. aureus interference for J8-based vaccines. Immunogenicity ranked J8 > J8i ≈ J8i-J8i > p145. NTD and CTD2 antisera demonstrated opsonic activity, indicating protective potential. PADRE–J8 conjugates significantly enhanced antibody magnitude and quality, producing strong opsonic bactericidal responses against both standard and p145-mutant GAS strains. PADRE–J8i was effective only against standard strains. This is the first report to suggest at least two B-cell epitopes within the J8i peptide. Conclusion: These findings support the diagnostic utility of p145, NTD, and CTD2 under co-infection settings, and the vaccine potential of J8, NTD, and CTD2, particularly when conjugated to a T helper for enhanced antigen presentation. Full article

Background: Sepsis remains a significant cause of morbidity and mortality in preterm and low birth weight (LBW) neonates, especially in low- and middle-income countries (LMICs). Lactoferrin, a glycoprotein present in breast milk with antimicrobial activity, is a low-cost, readily available, and promising intervention currently under investigation. The available literature presents conflicting results on the impact of lactoferrin on the risk of late-onset sepsis (LOS). This study evaluated the effectiveness of two doses of bovine lactoferrin (bLF) supplementation in preventing LOS and necrotizing enterocolitis (NEC) in preterm and LBW neonates in Pakistan. Methods: A three-arm, double-blind, placebo-controlled, randomized clinical trial in the neonatal intensive care unit of Aga Khan University was conducted from July 2019 to August 2020. Preterm (28 to 36 + 5 weeks gestational age) and low birth weight (≥1000 g to <2500 g) neonates who established enteral feeding by 72 h were eligible. The exclusion criteria included sepsis before randomization, maternal history of chorioamnionitis or group B streptococcus colonization, and congenital anomalies. Enrolled neonates were randomly assigned in a 1:1:1 ratio using a computer-generated random allocation sequence to receive placebo (D-glucose), 150 mg bLF, or 300 mg bLF mixed with breast milk once daily for 28 days. The study staff, parents, and outcome assessors were blinded to the allocation. The primary outcome was late-onset sepsis from the trial entry to 28 days. The secondary outcome was NEC from the trial entry to 28 days. Neonates were followed weekly for 28 ± 2 days, and episodes of LOS and NEC were recorded. Results: Of 305 neonates enrolled, 102, 102, and 101, respectively, were randomized to receive a placebo (arm A), 150 mg bLF (arm B), and 300 mg bLF (arm C), respectively. Outcome data of 291 participants (99 in arm A, 95 in arm B, and 97 in arm C) were available for inclusion in the intention-to-treat analysis. The frequency of culture-proven sepsis was 8/102 (7.8%) in arm A compared to 1/102 (0.98%) (p = 0.020) in arm B and 5/101 (4.9%) in arm C (p = 0.390). We did not find any difference in episodes of NEC between arms A (n = 3, 3%) and B (n = 0, 0%) (p = 0.087) or between arms A and C (n = 2, 2%) (p = 0.650). We reported compliance rates of 79 (79.79%) in arm A, 78 (82.1%) in arm B, and 82 (84.53%) in arm C for investigational products. Arm C recorded two deaths, but neither was attributed to the intervention. Conclusions: Bovine lactoferrin supplementation did not prevent late-onset sepsis in neonates of preterm and low birth weight in our trial. However, given the small sample size, further trials with larger sample sizes are required to investigate its efficacy in these at-risk groups. Full article

Berberine and carvacrol have demonstrated anti-inflammatory effects; however, their therapeutic potential in endometritis remains unclear. (Aims) This study aimed to examine the anti-inflammatory properties of berberine and carvacrol in a murine model of endometritis, with a focus on the underlying molecular mechanisms. (Main methods) The model was established via vaginal instillation of 0.1 mL of a mixture containing Escherichia coli, Staphylococcus aureus, and Group B Streptococcus, followed by treatment with 0.1 mL of berberine (4 mg/mL) and carvacrol (0.125 mg/mL) six days post-infection. All mice were euthanized on day 13, and uterine tissues were collected for subsequent analyses. (Key findings) Treatment with berberine and carvacrol significantly reduced tissue injury associated with endometritis, decreased mRNA expression of TLR2 and TLR4 (p < 0.01), and inhibited the phosphorylation of NF-κB and MAPK pathway-associated proteins, as well as the mRNA expression and levels of pro-inflammatory cytokines. (Significance) Berberine and carvacrol exhibit significant therapeutic effects against bacterial-induced endometritis by reducing TLR2 and TLR4 expression, inhibiting NF-κB and MAPK pathway activation, and decreasing pro-inflammatory cytokine production, thus demonstrating robust anti-inflammatory activity. Full article

Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations and the safety and efficacy profiles of maternal vaccines, including influenza, tetanus–diphtheria–acellular pertussis (Tdap), respiratory syncytial virus (RSV), COVID-19, and hepatitis B. Additionally, we analyze the barriers to maternal immunization, such as misinformation, vaccine hesitancy, and disparities in healthcare access, while exploring potential strategies to overcome these challenges through targeted educational initiatives, improved provider communication, and policy-driven interventions aimed at increasing vaccine confidence and accessibility. Finally, this review highlights recent innovations and future directions in maternal immunization, including emerging vaccines for Group B Streptococcus and cytomegalovirus. Expanding immunization programs and advancing research on maternal–fetal immunity are essential to optimizing vaccination strategies, improving public health outcomes, and reducing the global burden of infectious diseases. Full article

In this study, we added Bacillus licheniformis to the diet of hybrid sturgeon (Acipenser baerii ♀ Acipenser schrenkii ♂) to determine its effects on growth performance, blood physical and chemical indices and intestinal microflora composition. One hundred and sixty adult hybrid sturgeon were selected and fed with four types of diets (equal nitrogen and fat levels) that were respectively supplemented with 0.00% (control group), 0.10% (Group B), 0.20% (Group C) and 0.40% (Group D) B. licheniformis for 120 days. Results showed that the fish in group C had the highest final body weight, weight gain rate and specific growth rate (p < 0.05). The feed coefficients, crude protein and crude fat of group B, group C and group D were significantly lower than that of group A (p < 0.05). And the crude protein (CP) and crude fat (EE) in groups B, C and D were significantly higher than the control group (p < 0.05). The serum TC and TG, ALP, ALT, AST and GLU contents in the B. licheniformis-added groups were also significantly higher than those of the control group (p < 0.05). In addition, Cetobacterium was the dominant bacterial taxon in each group. With increasing the content of B. licheniformis in the diet, the Cetobacterium content decreased and the Plesiomonas content increased correspondingly. Adding B. licheniformis to the diet greatly decreased the abundance of Streptococcus, Candidatus Competibacter and Lactococcus. Our results indicated that appropriately adding (0.20%) B. licheniformis could increase growth, reduce the feed coefficient and increase the diversity of the intestinal microbiota of hybrid sturgeon. Full article

Background: Antimicrobial therapies used for treating group B streptococcus (GBS) early-onset sepsis (EOS) provide insight into clinicians’ adherence to antimicrobial stewardship (AMS) guidelines. Methods: We reviewed antimicrobial therapies given to treat newborns with GBS-EOS. Data were obtained from an Italian surveillance network (including 35 birthing centers) and were prospectively collected from 1 January 2003 to 31 December 2024. Empiric and definitive therapies were classified as adequate and inadequate. Results: There were 967,054 live births and 200 cases of GBS-EOS, of which 43 (21.5%) were preterm and 157 (78.5%) were full-term; 35 (17.5%) out of 200 showed no signs of illness. Fourteen (7.0%) died (one full-term and thirteen preterm newborns under 34 weeks of gestation). Based on the available information, antibiotics were adequate in 106/137 (77.4%) empiric and 48/119 (40.3%) definitive therapies. The duration of antibiotic courses did not differ between severe (median 10 days, IQR 8.0–14.0) and non-severe cases (median: 10 days; IQR: 10.0–12.5; p = 0.68). Antibiotic treatments lasted ≥ 15 days in 34 (20.1%) out of 169 cases with available information. Conclusions: In this large Italian multicenter study, deviations from international recommendations in antimicrobial therapies for GBS-EOS were critical. Our findings underscore the importance of timely antimicrobial de-escalation and the need to avoid excessively prolonged courses of antimicrobials. Full article

Natural toothpastes were introduced to limit the use of chemical ingredients commonly found in conventional toothpastes. The purpose of this in vitro study was to evaluate the antimicrobial properties of three developed natural toothpastes containing different antimicrobial agents: (a) Biosecur Organic Oral Care (BOOC), (b) Microsilver BG, and (c) Cranberry LG. These toothpastes were compared with a natural toothpaste of the same composition but without any added natural antimicrobial agent (negative control), as well as with a commercial synthetic toothpaste (positive control). The antimicrobial properties of the toothpastes were assessed using the disc diffusion test against three oral pathogens: Candida albicans, Streptococcus mutans, and Prevotella intermedia. Each tested toothpaste sample was placed in Petri dishes, where specific microorganisms selected for the study were cultivated. After incubation, the circular area formed around the discs (diameter), known as the inhibition zone, was measured demonstrating the inhibitory effect of the product on the microorganisms used in the efficacy test. All the experimental toothpastes exhibited higher antimicrobial properties compared to the negative control group, except for Streptococcus mutans, where only BOOC-containing toothpaste presented significant higher inhibition zones (p < 0.001). Considering the outcomes of the antimicrobial property test, the most effective natural experimental toothpaste was the BOOC-containing one, which showed better antimicrobial behavior even from the commercially available synthetic toothpaste (positive control). The tested natural antimicrobial agents were effective for enhancing the antimicrobial properties of the experimental toothpastes that were included, especially Biosecur Organic Oral Care agent. Full article

Background: An imbalance in the vaginal microbiota, often characterized by reduced lactobacilli, paves the way forth for opportunistic bacteria from the gastrointestinal tract. The presence of aerobic bacteria in the genital tract during pregnancy can have negative outcomes on the pregnancy. Peripartum infections, when not adequately managed, can significantly impact maternal and neonatal health. Antimicrobial resistance poses an escalating global health threat, with newborns particularly vulnerable. Methods: This study constitutes a retrospective observational analysis, encompassing all microbial strains isolated from pregnant women admitted to the “Pius Brînzeu” Clinical County Emergency Hospital in Timișoara, Romania for various infectious diseases over one year. We analyzed 274 samples from 246 pregnant women, of which 242 were cervical samples, 23 urine cultures, 3 wound secretions, 3 amniotic fluids, 1 peritoneal cavity fluid, 1 sputum, and 1 hemoculture. Results: In cervical samples, Group B Streptococcus (GBS) was the most prevalent, representing 42.46% of the isolates. E. coli was the second most frequent at 30.16%, followed by K. pneumoniae at 11.9%, S. aureus at 8.73%, C. albicans at 2.78%, and other species at 3.97%. A total of 9.63% of cervical GBS isolates exhibited resistance to penicillin, while 23.36% were identified as multi-drug resistant (MDR). Methicillin-resistant S. aureus (MRSA) and MDR S. aureus strains were identified in 50% and 54.54% of the S. aureus-positive cervical samples, respectively. Conclusions: Recognizing the implications of maternal infection or colonization, especially with antimicrobial resistance bacteria, aids in assessing risks during pregnancy. Full article

This study evaluated the differential expression of four placental markers—vitamin D receptor (VDR), Cluster of Differentiation 44 (CD44), osteopontin (OPN), and cyclooxygenase-2 (COX-2)—in response to pathogens, which may contribute to our understanding of pathogen-specific impacts on pregnancy outcomes. We immunohistochemically (IHC) analyzed placental tissues obtained from 70 healthy-term pregnant women in the control group and compared them to tissues obtained from 78 women with pregnancy above 24 weeks of gestation, single-pathogen vaginal infection, and premature rupture of membranes/preterm premature rupture of membranes (PROM/PPROM). We detected high expression of these four molecules in cases of Group B Streptococcus (GBS) and Ureaplasma urealyticum vaginal infections, and moderate expression in cases of Enterobacteriaceae infections, except for Klebsiella; the cases with Klebsiella and Candida species (spp.) vaginitis exhibited a lower expression compared to the healthy control group. VDR, CD44, and OPN had increased placental expression in GBS and Ureaplasma urealyticum vaginal infections; the opportunistic pathogenicity of both Escherichia coli and Candida spp. explains their low IHC positivity, and the tremendous ability of Gram-negative bacteria to elude the host immunity is revealed by the negative IHC staining in cases of Klebsiella vaginitis. These findings suggest that pathogen-specific alterations in the expression of these markers may contribute to the differential risk stratification of pregnancy complications and may mitigate the risks of adverse maternal and fetal outcomes. Interventions aiming to modulate these pathways might improve pregnancy outcomes. Full article

Streptococcus agalactiae, known as group B streptococci (GBS), colonizes the digestive and genitourinary tracts and causes neonatal diseases and infections in immunocompromised and elderly individuals. GBS neonatal disease prevention includes intrapartum antibiotic prophylaxis. We characterized 101 GBS isolates obtained from patients in João Pessoa, northeastern Brazil, owing to the need to develop and implement vaccines to prevent GBS infections. Capsular types were determined using multiplex-PCR, and antibiotic susceptibility profiles were determined using disc diffusion or the gradient strip method. Clonal diversity was evaluated using pulsed-field gel electrophoresis. Fourteen selected isolates had the genome sequenced and evaluated for virulence and resistance genes. The GBS population had high clonal diversity, with serotype Ia and V prevalence. Among the sequenced isolates, we detected antibiotic resistance genes (ant(6)-Ia, catA8, ermA, ermB, lsaE, lsnuB, mefA/msrD, tetM, tetO, and tetS), several virulence genes, and mobile genetic elements integrated into the chromosome. The most frequent Sequence Type (ST) was ST144, followed by ST196, ST28, ST19, ST12, ST23, ST103, and the new ST1983 (CC103). Phylogenetically, ST103 and ST1983 were distant from the other STs. Our data revealed highly virulent GBS strains in this population and a new ST that could be related to a zoonotic origin. Full article

Background/objectives: Streptococcus agalactiae (or Group B Streptococcus, GBS) is a major cause of neonatal meningitis globally. There are 10 serotypes of GBS, which are distinguished by their capsular polysaccharide (CPS) structure, with serotypes Ia, Ib, II, III, IV and V responsible for up to 99% of infections. Currently, there are no licensed vaccines against GBS. The most developed candidates are glycoconjugate vaccines, which can be highly effective but are also expensive to produce by existing approaches and unaffordable for many parts of the world. Biosynthesis of recombinant glycans and glycoconjugates in tractable strains of bacteria offers a low-cost alternative approach to current chemical conjugation methods. Methods: In this study, we apply combinatorial hierarchical DNA assembly to the heterologous biosynthesis of GBS III, IV and V CPSs in E. coli. Each gene was removed from its native regulation, paired with synthetic regulatory elements and rebuilt from the bottom up to generate libraries of reconstituted pathways. These pathways were screened for glycan biosynthesis using serotype-specific antisera. Results: We identified several configurations that successfully biosynthesised the GBS CPSs. Furthermore, we exploited the conserved nature of the GBS CPS biosynthesis loci and the flexibility of modular DNA assembly by constructing hybrid pathways from a minimal pool of glycosyltransferase genes. We show that transferase genes with homologous function can be used interchangeably between pathways, obviating the need to clone a complete locus for each new CPS assembly. Conclusions: In conclusion, we report the first demonstration of heterologous GBS CPS IV and V biosynthesis in E. coli, a key milestone towards the development of low-cost recombinant multivalent GBS glycoconjugate vaccines. Full article