Publications by authors named "Paul Heath"

Neonatal sepsis causes substantial morbidity and mortality, the burden of which is carried by low-income countries (LICs). The emergence of multidrug-resistant pathogens in vulnerable neonatal populations poses an urgent threat to infant survival. spp.

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  • The study investigates the safety and immunogenicity of a TdaP vaccine for pregnant women living with HIV, aiming to protect infants from severe pertussis disease.
  • Conducted in Uganda, the trial randomly assigned 181 women (HIV-positive and HIV-negative) to receive either the TdaP or Td vaccine, evaluating immune responses in infants post-delivery.
  • Findings will provide valuable insights into the vaccine's effectiveness and safety for this specific population, contributing to better health outcomes for mothers and their babies.
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Background: Vaccination during pregnancy is an important healthcare intervention for safeguarding the health of the mother and their infants. Ethnic disparities in recruitment to vaccine research studies during pregnancy potentially contribute to health inequalities. The aim of the current study was to explore the barriers and enablers influencing the willingness of pregnant women from ethnic minority backgrounds to participate in vaccine research studies.

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  • Primary biliary cholangitis (PBC) is a liver and immune system condition, and a study investigated the effects of transplanting autologous bone marrow-derived mononuclear cells (BM-MNCs) in affected patients.
  • Sixteen PBC patients underwent BM-MNC harvesting and transplantation between 2017 and 2022, with monitoring of liver function and immune cell changes over time using statistical analyses.
  • The results showed significant improvements in liver function tests and notable changes in immune cell populations, suggesting that BM-MNC transplantation could be a promising therapeutic approach for managing PBC.
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Background: Group B streptococcus (GBS) remains a leading cause of infant sepsis, meningitis and death despite intrapartum antibiotic prophylaxis. A vaccine is urgently required, and two candidates are in advanced clinical trials. For successful GBS vaccine implementation, especially if a vaccine is licensed based on an immunological threshold, there must be cross-sector engagement, effective advocacy, robust plans for phase IV studies and equitable access.

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  • The study aimed to compare the immune responses of preterm infants receiving a meningococcal B vaccine using either a 2+1 or a 3+1 vaccination schedule while also evaluating the side effects of routine vaccinations.
  • The research was conducted in an open-label, phase IV study format across six hospitals in the UK, enrolling 129 preterm infants born before 35 weeks gestation.
  • Results indicated that while both vaccination schedules were effective, the 3+1 schedule led to a significantly higher antibody response against a specific strain compared to the 2+1 schedule, but also resulted in more fever episodes after vaccination.
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The growing understanding of the role of extracellular vesicles (EVs) in embryo-maternal communication has sparked considerable interest in their therapeutic potential within assisted reproductive technology, particularly in enhancing implantation success. However, the major obstacle remains the large-scale production of EVs, and there is still a gap in understanding how different culture systems affect the characteristics of the EVs. In the current study, trophoblast analogue human chorionic carcinoma cell line was cultivated in both conventional monolayer culture (2D) and as spheroids in suspension culture (3D) and how the cell growth environment affects the physical, biochemical and cellular signalling properties of EVs produced by them was studied.

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Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs.

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Age-associated deep-subcortical white matter lesions (DSCLs) are an independent risk factor for dementia, displaying high levels of CD68 microglia. This study aimed to characterize the transcriptomic profile of microglia in DSCLs and surrounding radiologically normal-appearing white matter (NAWM) compared to non-lesional control white matter. CD68 microglia were isolated from white matter groups ( = 4 cases per group) from the Cognitive Function and Ageing Study neuropathology cohort using immuno-laser capture microdissection.

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Background: Invasive meningococcal disease (IMD) is most common in the first year of life. We hypothesized that preterm infants may have a higher risk of IMD and more severe disease than term infants. We compared the incidence, demographics, clinical presentation, and outcomes of IMD in preterm compared with term infants during the first 5 years after implementation of a national meningococcal group B vaccine (4CMenB) for infants in England.

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Introduction: Capsular polysaccharide (CPS) serotype-specific Immunoglobulin G (IgG) in cord blood has been proposed as a correlate of protection against invasive Group B Streptococcus (iGBS) disease. Although protective levels are required in infants throughout the window of vulnerability up to 3 months of age, little is known regarding the kinetics of GBS-specific IgG over this period.

Methods: We enrolled 33 healthy infants born to mothers colonized with GBS.

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Introduction: Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received.

Methods: Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria.

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To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain.

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Amyotrophic lateral sclerosis is a fatal neurodegenerative disease, associated with the degeneration of both upper and lower motor neurons of the motor cortex, brainstem and spinal cord. Death in most patients results from respiratory failure within 3-4 years from symptom onset. However, due to disease heterogeneity some individuals survive only months from symptom onset while others live for several years.

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Transmission of human cytomegalovirus (CMV), from a pregnant woman to her fetus can cause congenital CMV infection, with life-long problems in some infected children. The presence of CMV in an infected individual's bodily fluid is known as shedding. An individual can become infected with CMV through contact with another individual who is shedding CMV in their bodily fluid, and the avoidance of contact with infected fluids may reduce the risk of infection.

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  • * The follow-up study measured the immune responses of 40 participants at 1.5 and 2.5 years after vaccination, focusing on serum bactericidal antibody (SBA) levels against various MenB strains and other serogroups.
  • * Results showed that while antibody levels declined over time, a significant percentage (68.8% for MenB and up to 87.5% for MenA, W, and Y) maintained protective antibody levels, with MenC showing a quicker decline.
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  • - The study aimed to evaluate two antiseptic methods for skin disinfection before inserting central venous catheters in preterm infants, as catheter-related sepsis (CRS) poses serious health risks.
  • - Conducted across two neonatal intensive care units in the UK, the feasibility study involved 116 preterm babies and assessed various outcomes such as catheter colonisation, sepsis rates, and recruitment success.
  • - Results showed a low catheter colonisation rate of 5.2% and minimal incidents of sepsis, indicating that while a larger trial is possible, it may require many participants due to the low event rate.
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Objective: We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks' gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance.

Design And Setting: Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE).

Participants: All live births ≥34 weeks' gestation between September 2020 and August 2021.

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Introduction: During the SARS-CoV-2 pandemic, maternity care has been substantially altered to reduce transmission of the SARS-CoV-2 virus. Many antenatal services are now restricted or delivered online, and visiting has been restricted during labour and in the postnatal period.

Methods: We conducted an online survey from 1st August to 31st December 2020 to investigate the experiences of women who were pregnant or breastfeeding in the UK during the SARS-CoV-2 pandemic.

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  • The study investigated the safety and effectiveness of omicron BA.1 monovalent and bivalent booster vaccines compared to the original mRNA-1273 vaccine in a large, randomized trial involving participants aged 16 and older.
  • Conducted in the UK, the trial assessed antibody responses and safety profiles, focusing on the immune response at day 29 after administration of the boosters.
  • A total of 3,098 participants were enrolled, with results showing differing immune responses between the new omicron boosters and the original vaccine, aiming for both non-inferiority and potential superiority.
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Background: This was the first study to investigate the reactogenicity and immunogenicity of heterologous or fractional second dose COVID-19 vaccine regimens in adolescents.

Methods: A phase II, single-blind, multi-centre, randomised-controlled trial recruited across seven UK sites from September to November 2021, with follow-up visits to August 2022. Healthy 12-to-16 years olds were randomised (1:1:1) to either 30 µg BNT162b2 (BNT-30), 10 µg BNT162b2 (BNT-10), or NVX-CoV2373 (NVX), 8 weeks after a first 30 µg dose of BNT162b2.

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Background: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design.

Methods And Findings: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa).

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Background: Dietary supplementation with prebiotic oligosaccharides to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or very low birth weight (VLBW) infants.

Objectives: To assess the benefits and harms of enteral supplementation with prebiotics (versus placebo or no treatment) for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants.

Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care database and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to July 2022.

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