Neonatal Infection Research Articles

Frequency and characteristics of seizures precipitated by febrile urinary tract infections in neonates and infants

BackgroundA febrile urinary tract infection (UTI) is a minor febrile seizure (FS) determinant. Seizures precipitated by febrile UTIs in neonates and infants frequently surprise parents, as they are vulnerable to bacterial meningitis and younger than the usual ages of FS. However, their frequency and characteristics are relatively unknown. MethodsThis study screened 1059 children (≤12 months) with febrile UTIs admitted to Chonnam National University Children's Hospital from January 2015 to June 2023. Patients with seizures precipitated by febrile UTIs were enrolled, and their medical records were reviewed. The frequency and clinical characteristics of seizures effectuated by febrile UTIs were investigated by comparing FS, FS+, and afebrile seizure (aFS). ResultsTwenty-eight patients (2.6%) were enrolled: 19 with early-onset FS+ (2.3% of 814 patients <6 months), nine with FS (3.7% of 245 patients), but there were none with aFS. Acute pyelonephritis was found in 80.8% of 26 patients. Clustered seizures (47.4% vs. 22.2% in FS, P = 0.197) and complex types (73.7% vs. 22.2%; P = 0.015) were frequent in early-onset FS+. Among 42 seizure episodes, bilateral tonic seizures were noted only in FS+ (44.8%; P = 0.001), but bilateral tonic-clonic seizures were frequent in FS (69.2% vs. 27.6%; P = 0.011). ConclusionSeizures precipitated by febrile UTIs occurred in 2.6% of neonates and infants: all were febrile and were predominantly with acute pyelonephritis. Infantile FS characteristics of febrile UTIs resembled those of usual FS, whereas early-onset FS + differed significantly as usually occurring in complex types and bilateral tonic ones.

Multicentre external validation of the Neonatal Healthcare-associated infectiOn Prediction (NeoHoP) score: a retrospective case–control study

Background and objectivesNeonatal mortality due to severe bacterial infections is a pressing global issue, especially in low-middle-income countries (LMICs) with constrained healthcare resources. This study aims to validate the Neonatal...

The complete genome sequence of five pre-2013 Escherichia coli sequence type (ST)1193 strains reveals insights into an emerging pathogen.

Fluoroquinolone-resistant Escherichia coli sequence type (ST)1193 is a profound, emerging lineage associated with systemic, urinary tract and neonatal infections. Humans, companion animals and the environment are reservoirs for ST1193, which has been disseminated globally. Following its detection in 2007, ST1193 has been identified repeatedly amongst fluoroquinolone-resistant clones in Australia. However, despite the growing importance of ST1193, only three complete genomes are published in the literature, none of which are from Australia. Here we expand on the available ST1193 resources with the complete genomes of five ST1193 strains sequenced using Oxford Nanopore Technologies and Illumina. Using in silico genotyping, we found that all strains were multi-drug resistant, including resistances to fluoroquinolones and cephalosporins. In vitro antibiotic susceptibility testing mostly correlated with individual genotypes. The exception was MS8320, which had additional in vitro resistance to piperacillin/tazobactam, ampicillin/sulbactam, cefazolin and doripenem (carbapenem). Further investigation identified seven additional copies of an IS26 transposable unit carrying a bla TEM-1B beta-lactamase gene, suggesting this tandem amplification is associated with extended resistance phenotypes. Uropathogenicity factors, including three separate siderophore-encoding loci, were conserved in chromosomal and plasmid regions. Using all complete genomes, we further elucidated the recombination events surrounding the previously described K5/K1 capsular locus switch. Phenotypic confirmation of differing capsules in Australian ST1193 strains, coupled with genetic analysis revealing insertions downstream of the capsular locus, underscored the genetic distinctions between K5 and K1 capsule encoding strains. This study provides five new reference ST1193 genomes from Australia. These include the earliest complete K5-capsule ST1193 genomes on record (collected 2007), alongside our reference genome (MS10858), a clinical isolate obtained early during the ST1193 expansion and representative of the predominant K1-associated clade. These findings lay the foundations for further genomic and molecular analyses that may help understand the underlying reasons for the rapid global expansion of ST1193.

Seroprevalence of Neonatal Herpes Simplex Virus Infection at A Tertiary Teaching Hospital in Malaysia

INTRODUCTION: Neonatal herpes simplex virus (HSV) infection is generally infrequent, despite being a life-threatening illness. Knowledge of its prevalence is limited in Malaysia since most cases are asymptomatic infections and only limited routine neonatal HSV screening is conducted. This study therefore provides a comprehensive investigation of the seroprevalence of HSV-1 and HSV-2 in neonates. MATERIALS AND METHODS: Serological screening for HSV-1 IgG and HSV-2 IgG antibody tests using the Electrochemiluminescence assay was performed on serum samples of 215 neonates delivered from January until December 2022 at Hospital Universiti Sains Malaysia. RESULTS: Of the neonates, 54.4% were found to be HSV-1 positive, while 4.2% were HSV-2 positive. All the HSV-2 neonates were co-infected with HSV-1. Newborns aged 0–10 days were the most infected group by HSV-1 (92.3%) and HSV-2 (55.6%). The most reported clinical presentation was small gestational age (SGA) (60%). Microcephaly and macrocephaly were observed in one neonate each. The clinical presentations of reactive HSV-1 and HSV-2 cases revealed the presence of fever with rash in both cases. CONCLUSION: The high seroprevalence of HSV-1 is alarming. It is hoped that these data will support the advocacy of screening women for HSV before or during pregnancy as a precautionary approach to reducing the risk of vertical transmission.

Prevalence of bacterial vaginosis, sexually transmitted infections and their association with HPV infections in asymptomatic women attending antenatal care in Ethiopia.

Sexually transmitted infections (STIs) and human papillomavirus (HPV) infections are common among women of reproductive age and can lead to infertility, adverse pregnancy outcomes, neonatal infections and cervical cancer. In countries with limited medical coverage, untreated infections contribute to high morbidity. This study aimed to expand the current knowledge on the prevalence of bacterial vaginosis (BV) and STIs in pregnant Ethiopian women and assess the association of these conditions with HPV infections. Socio-demographic data and vaginal lavage samples were collected from 779 asymptomatic women aged 18 to 45 years (median age, 25.9 years) attending antenatal care in seven centres across Ethiopia. Multiplex polymerase chain reaction was used to test for BV, Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, herpes simplex virus types 1 and 2 (HSV-1/2), Mycoplasma, Ureaplasma, Candida species and HPV. Overall, 26.8% (95% confidence interval (CI): 23.7-29.9) of women tested positive for BV or one of the following STIs: C. trachomatis, T. vaginalis, N. gonorrhoeae, Mycoplasma genitalium, HSV-1/2 or Ureaplasma urealyticum. Additionally, 22.1% tested positive for at least one high-risk HPV type. Chlamydia trachomatis and HSV-2 were significantly more common among women who were positive for HPV and high-risk HPV. This study reveals a high prevalence of asymptomatic pregnant women who are positive for BV, STIs or HPV, putting them at risk of adverse pregnancy outcomes, secondary infertility or cervical cancer in a country with limited medical coverage. Screening and treating these women could be crucial in reducing morbidity.

Identifying the Impact of Chlamydia trachomatis Screening and Treatment on Mother-to-Child Transmission, and Respiratory Neonatal Outcomes in Mexico.

Chlamydia trachomatis (C. trachomatis) screening and treatment in pregnancy allows the opportunity to reduce adverse pregnancy and neonatal outcomes worldwide. Although C. trachomatis infection is easily treated and cured with antibiotics, only some countries have routine pregnancy screening and treatment programs. We therefore evaluated whether just one maternal screening for C. trachomatis is enough to prevent adverse pregnancy and negative neonatal outcomes. Among the 4087 first-time gynecological-obstetric consultations granted at the National Institute of Perinatology in 2018, we selected the study population according to a case-cohort design. Antenatal C. trachomatis screening and treatment interventions were performed on 628 pregnant women using COBAS® TaqMan CT. C. trachomatis DNA was also detected in samples from 157 infants of these mothers. In the maternal cohort, incidence of C. trachomatis infection was 10.5%. The vertical transmission rate was 1.5% for the cohort of mothers who tested positive for C. trachomatis and received treatment, and 29.7% for those with a negative test. By evaluating symptomatic neonatal infection, the hazard rate of perinatal pneumonia was 3.6 times higher in C. trachomatis-positive babies than in C. trachomatis-negative babies. Despite the low rate of mother-to-child transmission in women positive for C. trachomatis, possible maternal infection that is not detected in pregnancy significantly increases the risk of neonatal infection with consequent perinatal pneumonia.

Microneedle Transdermal Patches- A Novel Painless Approach with Improved Bioavailability for the Treatment of Diseases with Special Prevalence to Neonatal Infection.

Microneedle transdermal drug delivery systems (TDDS) present a compelling substitute for parenteral and oral administration methods in the treatment of several illnesses. The past several decades have seen a revolution in technology that has changed the production of micro-structured devices, including the development of microneedles for transdermal patches. These devices are used to deliver drugs, proteins, insulin, antibiotics, vaccinations, and other therapies through the skin. They are proven to be beneficial for the prevention of newborn infections. Successful treatments for conditions like cancer, diabetes, rheumatoid arthritis, Alzheimer’s disease, and migraines can be achieved with the use of transdermal microneedle patches. Microneedles have the potential to offer prolonged immunity, dosage sparing, and improved protection against viral challenges. The epidermis and dermis are immunologically rich layers, and because of the needles’ micron-size structure, these devices have shown to be significantly more effective at targeting these layers, indicating their potential utility in the creation of next-generation vaccines. Within the framework of developing vaccines. Microneedle transdermal patches’ main benefits are that they are easy to use, painless, and non-invasive. Here, we discuss the types of microneedle transdermal patches and how microneedle transdermal patches are now being used to treat infections in newborns and vaccination and as a more cost-effective self-administration approach. This also enhances the bioavailability when used in vaccination therapy. Next, we’ll go over how microneedle transdermal patches are currently used to treat a variety of illnesses effectively, including those that affect newborns.

Effects of a single oral dose of azithromycin in laboring women on antimicrobial resistance (AMR) and the microbiome: a protocol for the Antimicrobial Resistance Sub-Study of the A-PLUS trial

Background The Azithromycin Prevention in Labor Use Study (A-PLUS), a large, multi-national randomized trial, was performed to evaluate the improvement of maternal and newborn outcomes following a single dose of azithromycin (AZ) given during labor. However, the immediate and long-term impact of this single dose on the microbiome and the development or prevalence of antimicrobial resistance are unknown. We designed a sub-study to assess AZ resistance of bacterial isolates from clinical infections and of three target bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli) from the serial surveillance of the nasopharynx and rectum. Additionally, the serially surveilled samples will be evaluated for changes to the microbiome and the resistome of the nasopharynx and rectum. Methods and Analysis As part of the large, randomized APLUS trial, maternal and neonatal clinical infections were monitored for up to 42 days postpartum, and samples collected for culture using site-specific routine methods. For this sub-study, cultured bacterial isolates will be assessed for AZ resistance using an antibiotic susceptibility method. Additionally, a random subset of maternal-neonatal dyads from the main trial will be selected for serial surveillance with aseptic swab collections of the nasopharynx and the rectum at baseline, and subsequently at 1-week, 6-weeks, 3-months, 6-months, and 12-months postpartum. The serial samples will undergo selective culturing of sentinel bacterial species and screened for AZ resistance. An additional set of serial samples will be stored for future microbiome and resistome analyses. Ethics and Dissemination The study protocol was reviewed, and ethics approval obtained from all the relevant ethical review boards at each research site. All participants will provide informed written consent prior to their enrollment. Results of the trial will be disseminated through peer-reviewed publications, presentations at relevant conferences, and at dissemination meetings with the ministries of health and local stakeholders at each research site. Trial Registration NCT03871491.

Neonatal neutrophils exhibit reduced NLRP3 inflammasome activation

Abstract Newborns are at high risk to develop sepsis. This is linked to innate immune responses at birth which are not completely adapted to postnatal life. Neutrophils are key players of innate immunity and exhibit a marked ontogenetic regulation of their functionality. Here, we studied the NLRP3 inflammasome in neonatal neutrophils and found lower baseline expression of NLRP3, pro-caspase-1 and the K+-channel KV1.3 compared to adult neutrophils. Following stimulation with LPS/Nigericin, ASC oligomerization, caspase-1 activation and IL-1β release were significantly reduced in neonatal compared to adult neutrophils. Similarly, stimulation of neonatal neutrophils with E-selectin led to reduced NLRP3 inflammasome activation accompanied by diminished release of the alarmin S100A8/A9. Taken together, our results strongly indicate diminished NLRP3 inflammasome activation in neonatal neutrophils leading to a significant reduction of released IL-1β and S100A8/A9. These findings identify reduced neutrophil NLRP3 inflammasome activation as critical component contributing to the inherent susceptibility to infections in neonates.

Association between Congenital Anomalies and Late-Onset Bacterial Infections in Neonates Admitted to Neonatal Intensive Care Units in Australia and New Zealand: A Population-Based Cohort Study

Introduction: Compromised neonatal intensive care unit neonates are at risk of acquiring late-onset infections (late-onset sepsis [LOS]). Neonates born with congenital anomalies (CAs) could have an additional LOS risk. Methods: Utilising the population-based Australian and New Zealand Neonatal Network data from 2007 to 2017, bacterial LOS rates were determined in very preterm (VPT, <32 week), moderately preterm (MPT, 32–36 weeks), and term (FT, 37–41 weeks) neonates with or without CA. Stratified by major surgery, the association between CA and bacterial LOS was evaluated. Results: Of 102,808 neonates, 37.7%, 32.8%, and 29.6% were born VPT, MPT, and FT, respectively. Among these, 3.4% VPT, 7.5% MPT, and 16.2% FT neonates had CA. VPT neonates had the highest LOS rate (11.1%), compared to MPT (1.8%) and FT (1.8%) neonates. LOS rates were higher in CA neonates than those without (8.2% versus 5.1% adjusted relative risk [aRR] 1.67, 95% confidence interval [CI]: 1.45–1.92). Neonates with surgery had a higher LOS rate (14.2%) than neonates without surgery (4.4%, p < 0.001). Among the neonates without surgery, CA neonates had consistently higher LOS rates than those without CA (VPT 14.3% vs. 9.6% [aRR 1.32, 95% CI: 1.11–1.57]; MPT 4% vs. 0.9% [aRR 4.45, 95% CI: 3.23–6.14]; and FT 2% vs. 0.7% [aRR 2.87, 95% CI: 1.97–4.18]). For the neonates with surgery, CAs were not associated with additional LOS risks. Conclusion: Overall, we reported higher rates of LOS in neonates with CA compared to those without CA. Regardless of gestation, CA was associated with an increased LOS risk among non-surgical neonates. Optimisation of infection prevention strategies for CA neonates should be explored. Future studies are needed to evaluate if the infection risk is caused by CA or associated complications.

Transplacental Transmission of SARS-CoV-2: A Narrative Review.

Background and Objectives: The study aims to explore the potential for transplacental transmission of SARS-CoV-2, focusing on its pathophysiology, placental defense mechanisms, and the clinical implications for maternal and neonatal health. Materials and Methods: A comprehensive review of the current literature was conducted, analyzing studies on SARS-CoV-2 infection in pregnancy, the expression of key viral receptors (ACE2 and TMPRSS2) in placental cells, and the immune responses involved in placental defense. The review also examined the clinical outcomes related to maternal and neonatal health, including adverse pregnancy outcomes and neonatal infection. Results: The expression of ACE2 and TMPRSS2 in the placenta supports the biological plausibility of SARS-CoV-2 transplacental transmission. Histopathological findings from the infected placentas reveal inflammation, vascular changes, and the evidence of viral particles in placental tissues. Clinical reports indicate an increased risk of preterm birth, intrauterine growth restriction, and neonatal infection in pregnancies affected by COVID-19. However, the frequency and mechanisms of vertical transmission remain variable across studies, highlighting the need for standardized research protocols. Conclusions: SARS-CoV-2 can potentially infect placental cells, leading to adverse pregnancy outcomes and neonatal infection. While evidence of transplacental transmission has been documented, the risk and mechanisms are not fully understood. Ongoing research is essential to clarify these aspects and inform obstetric care practices to improve maternal and neonatal outcomes during the COVID-19 pandemic.

Phenotypic bacterial epidemiology and antimicrobial resistance profiles in neonatal sepsis at Jimma medical center, Ethiopia: Insights from prospective study.

Epidemiological profiles and the rundown crisis of antimicrobial resistance from bacterial isolates in neonatal sepsis compel regular surveillance to enhance data-driven decision-making. Accordingly, this study aimed to assess the phenotypic epidemiology and antimicrobial resistance profiles of bacteria isolated from clinically suspected neonatal sepsis in Ethiopia. A total of 342 neonates suspected of clinical sepsis were randomly included in a prospective observational study conducted at the neonatal intensive care unit (NICU) of Jimma medical center (JMC) from May 2022 to July 2023. Blood samples were collected from each neonate and subjected to a culture test for identification of bacterial isolates and their antibiotic resistance profiles following the standardized guidelines. The laboratory results, along with relevant clinical data, were recorded using WHONET and analyzed using STATA software. Out of the 342 blood samples that were analyzed, 138 samples (40.4%, 95% CI: 35.1-45.6, P<0.01) exhibited proven bacterial infection. The infection rates were notably higher in males with 85/138 (61.6%, 95% CI: 53.4-69.8, P<0.01) and neonates aged 0-3 days with 81/138 (58.7%, 95% CI: 50.5-66.9, P<0.01). The majority of the infections were attributed to Gram-negative bacteria, accounting for 101/138(73.2%, 95% CI: 65.6-80.7) cases, with 69/101(68.3%, 95% CI: 63.8-72.8) cases involving ESBL-producing strains, while Gram-positive bacteria were responsible for 26.8% (95% CI: 19.3-34.4) of the infections. The predominant isolates included Klebsiella pneumoniae (37.7%, 95% CI: 29.6-45.8), Coagulase-negative Staphylococci (CoNs) (20.3%, 95% CI: 13.6-27.0), and Acinetobacter species (11.6%, 95% CI: 6.0-17.1). Of the total cases, 43/72 (59.7%, 95% CI: 48.4-71.1, P<0.01) resulted in mortality, with 28/72 (38.9%, 95% CI: 27.70-50.1, P<0.03) deaths linked to Extended-Spectrum Beta-Lactamase (ESBL)-producing strains. Klebsiella pneumoniae displayed high resistance rates to trimethoprim-sulfamethoxazole (100%), ceftriaxone (100%), cefotaxime (98.1%), ceftazidime (90.4%), and gentamicin (84.6%). Acinetobacter species showed resistance to ampicillin (100%), cefotaxime (100%), trimethoprim-sulfamethoxazole (75%), ceftazidime (68.8%), chloramphenicol (68.8%), and ceftriaxone (68.8%). Likewise, CoNs displayed resistance to ampicillin (100%), penicillin (100%), cefotaxime (86.0%), gentamicin (57.2%), and oxacillin (32.2%). Multidrug resistance was observed in 88.4% (95% CI: 81.8-93.0) of isolates, with ESBL-producers significantly contributing (49.3%, 95% CI: 45.1-53.5). Furthermore, 23.0% (95% CI: 15.8-31.6) exhibited a prevalent resistance pattern to seven distinct antibiotic classes. The prevalence and mortality rates of neonatal sepsis were significantly high at JMC, with a notable surge in antibiotic and multidrug resistance among bacterial strains isolated from infected neonates, specifically ESBL-producers. These resistant strains have a significant impact on infection rates and resistance profiles, highlighting the requisite for enhanced diagnostic and antimicrobial stewardship, stringent infection control, and further molecular characterization of isolates to enhance neonatal survival.

Multidrug Resistant Group B Streptococcus Isolates from Pregnant Women in Delta State, Nigeria.

&lt;b&gt;Background and Objective:&lt;/b&gt; Group B &lt;i&gt;Streptococci&lt;/i&gt; (GBS) are globally recognized as a major risk factor for neonatal infections and various obstetric complications. More so, biofilm formation has been suggested to be important for GBS pathogenesis. The aim of this study was to determine the prevalence and antibiotic susceptibility pattern of GBS among pregnant women and their capacity to form biofilm. &lt;b&gt;Materials and Methods:&lt;/b&gt; A total of 87 pregnant women at 34 to 37 weeks' gestation aged 17-45 years were recruited from 3 healthcare centres in Delta State, Nigeria. Cultures for the isolation of GBS were carried out using recto-vaginal swabs, according to standard microbiological methods. All strains isolated were used for susceptibility tests to various antibiotics as recommended by CLSI using the disk-diffusion method. &lt;b&gt;Results:&lt;/b&gt; The overall prevalence of GBS colonization among pregnant women was 43.6% (38/87). The &lt;u&gt;<&lt;/u&gt;30 age group had the highest rate of GBS colonization. Resistance to erythromycin and vancomycin was 48.2 and 66.4%, respectively. The fluoroquinolones had the lowest resistant rates with no isolate showing resistance to ofloxacin. Multidrug resistance (MDR) (&lt;u&gt;>&lt;/u&gt;3 drug classes) was detected in 73.7% (28/38) of the GBS isolates. All GBS isolated in this study were either strong, moderate or weak biofilm producers. However, most 28 (73.7%) were strong biofilm producers. Resistance of GBS isolates to erythromycin and vancomycin, drugs used for treating GBS infection was high. &lt;b&gt;Conclusion:&lt;/b&gt; This suggested the importance of testing antimicrobial susceptibilities in GBS colonized pregnant women in order to guide antibiotic therapy and minimize newborn infection and co-morbidity.

Genomic approach to determine sources of neonatal Staphylococcus aureus infection from carriage in the Gambia

Staphylococcus aureus is a major cause of neonatal infections in various anatomical sites, resulting in high morbidity and mortality in The Gambia. These clinical infections are often preceded by nasal carriage of S. aureus, a known risk factor. To determine whether potential sources of newborn S. aureus infections were from carriage, and to characterize S. aureus present in different anatomical sites (blood, ear, eye, umbilical cord, skin, pus, oropharynx, breast milk and vagina), we performed whole-genome sequencing of 172 isolates from clinical sites as well as from healthy and unhealthy carriage. A random selection of mothers (n = 90) and newborns (n = 42) participating in a clinical trial and testing positive for S. aureus were considered for this study. Sequence data were analyzed to determine S. aureus multilocus sequence types and selected antimicrobial and virulence gene profiles. Our findings revealed that in The Gambia, ST15 is the dominant sequence type associated with both carriage and clinical infection. In addition, S. aureus isolates causing clinical infection among neonates were genetically similar to those colonizing their oropharynx, and the different anatomical sites were not found to be uniquely colonized by S. aureus of a single genomic profile. Furthermore, while S. aureus associated with clinical infection had similar antimicrobial resistance gene profiles to carriage isolates, only hemolysin and adhesive factor virulence genes were significantly higher among clinical isolates. In conclusion, this study confirmed S. aureus oropharyngeal colonization among neonates as a potential source of clinical infection in The Gambia. Hence, interventions aiming to reduce neonatal clinical infections in The Gambia should consider decreasing oropharyngeal S. aureus carriage.Trial registration The trial was registered at ClinicalTrials.gov NCT03199547.

Immunogenicity and protective efficacy of a recombinant lactococcus lactis vaccine against HSV-1 infection

BackgroundHerpes simplex virus type 1 (HSV-1) is a major cause of viral encephalitis, genital mucosal infections, and neonatal infections. Lactococcus lactis (L. lactis) has been proven to be an effective vehicle for delivering protein antigens and stimulating both mucosal and systemic immune responses. In this study, we constructed a recombinant L. lactis system expressing the protective antigen glycoprotein D (gD) of HSV-1.ResultsTo improve the stability and persistence of antigen stimulation of the local mucosa, we inserted the immunologic adjuvant interleukin (IL)-2 and the Fc fragment of IgG into the expression system, and a recombinant L. lactis named NZ3900-gD-IL-2-Fc was constructed. By utilizing this recombinant L. lactis strain to elicit an immune response and evaluate the protective effect in mice, the recombinant L. lactis vaccine induced a significant increase in specific neutralizing antibodies, IgG, IgA, interferon-γ, and IL-4 levels in the serum of mice. Furthermore, in comparison to the mice in the control group, the vaccine also enhanced the proliferation levels of lymphocytes in response to gD. Moreover, recombinant L. lactis expressing gD significantly boosted nonspecific immune reactions in mice through the activation of immune-related genes. Furthermore, following the HSV-1 challenge of the murine lung mucosa, mice inoculated with the experimental vaccine exhibited less lung damage than control mice.ConclusionOur study presents a novel method for constructing a recombinant vaccine using the food-grade, non-pathogenic, and non-commercial bacterium L. lactis. The findings indicate that this recombinant vaccine shows promise in preventing HSV-1 infection in mice.

Maternal Streptococcus agalactiae colonization in Europe: data from the multi-center DEVANI study.

Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine.

KLUYVERA CRYOCRESCENS URINARY TRACT INFECTION IN A NEONATE: A CASE REPORT AND LITERATURE REVIEW.

This case report details the fourth documented case of urinary tract infection caused by Kluyvera cryocrescens and the first in a neonate. Including a brief literature review on urinary tract infections associated with this organism, the report highlights the importance of considering uncommon pathogens in neonatal infections and the necessity of a thorough diagnostic approach to initiate appropriate antimicrobial treatment.

PhoP/PhoQ Two-Component System Contributes to Intestinal Inflammation Induced by Cronobacter sakazakii in Neonatal Mice.

Cronobacter sakazakii (C. sakazakii) is a foodborne pathogen capable of causing severe infections in newborns. The PhoP/PhoQ two-component system exerts a significant influence on bacterial virulence. This study aimed to investigate the impact of the PhoP/PhoQ system on intestinal inflammation in neonatal mice induced by C. sakazakii. Neonatal mice were infected orally by C. sakazakii BAA-894 (WT), a phoPQ-gene-deletion strain (ΔphoPQ), and a complementation strain (ΔphoPQC), and the intestinal inflammation in the mice was monitored. Deletion of the phoPQ gene reduced the viable count of C. sakazakii in the ileum and alleviated intestinal tissue damage. Moreover, caspase-3 activity in the ileum of the WT- and ΔphoPQC-infected mice was significantly elevated compared to that of the ΔphoPQ and control groups. ELISA results showed elevated levels of TNF-α and IL-6 in the ileum of the mice infected with WT and ΔphoPQC. In addition, deletion of the phoPQ gene in C. sakazakii resulted in a down-regulation of inflammatory genes (IL-1β, TNF-α, IL-6, NF-κB p65, TLR4) within the ileum and decreased inflammation by modulating the TLR4/NF-κB pathway. It is suggested that targeting the PhoP/PhoQ two-component system could be a potential strategy for mitigating C. sakazakii-induced neonatal infections.

Pregnancy outcomes among women with inflammatory bowel disease: A UK tertiary centre experience.

Optimal management of inflammatory bowel disease (IBD) in pregnancy is associated with better pregnancy outcomes. We describe management of IBD during pregnancy and maternal and fetal outcomes of patients from a tertiary UK IBD centre. This is a retrospective observational cohort study of all pregnancies occurring between 2015 and 2021 in a large tertiary IBD centre in the UK. IBD activity and management prior to, during and after pregnancy were recorded along with pregnancy and neonatal outcomes. Associations between IBD-focused interventions and any adverse pregnancy outcomes, as well as the association between IBD severity and treatments and adverse maternofetal outcomes were assessed. Pregnancies in 130 women with IBD were included for analysis. The mean maternal age at delivery was 30.5 (± 4.7) years. At conception, 73 women (56.2%) were in clinical remission and 24 (18.4%) were treated with a biologic agent. Active disease during pregnancy, measured by physician global assessment, was less frequent in women who were in clinical remission at conception, compared to those not in remission at conception (16/73 21.9% vs. 39/49 79.6%; data insufficient for eight women). Active IBD at conception was associated with pre-term birth (p = 0.04). Maternal corticosteroid use in any trimester was associated with low birth weight (T1 p = 0.02; T2 p = 0.005; T3 p = 0.007). Active disease (p = 0.008) and steroid use in the third trimester (p = 0.05) were both associated with neonatal infections up to sixmonths after birth. Women in clinical remission at the time of conception have favorable outcomes, consistent with prospective observational studies. Our observations emphasize the importance of high quality IBD care for women pre and post-partum in line with international recommendations.

Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71

Human Enterovirus 71 (EV71) has emerged as one of the predominant causative agents of hand, foot and mouth disease (HFMD) with global impact. Despite the inactivated vaccine being licensed, other vaccine candidates based on advanced technology platforms are under development. In this report, we rationally designed and constructed two DNA-launched live attenuated vaccine candidates (pDL-EV71) under the control of specific promoters. In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71. More importantly, the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR−/− mice, demonstrating its safety profile. Moreover, a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice. A single-dose immunization with 10 ​μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice. Overall, our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.