and browndOR: 1.1 to 0.9; 1.5). These estimates were not significantly altered in models including variables related to life-course SEP. Conclusion In this Brazilian population, UL risk increased with the darkening of skin colour, and the life-course SEP did not mediate this association.
Background: Progress has been made in reduction of under five mortality in India, however, neonatal mortality is reducing at a slower rate. Efforts are required to bring down neonatal mortality in order to attain the SDG-3. Prevention of sepsis among the high risk, vulnerable low birth weight neonates by a newer intervention with probiotic supplementation is promising.Methods/design: A phase III, multicentre, randomized, double blind, placebo-controlled is being conducted at six sites in India. A total of 6144 Healthy LBW infants fulfilling the eligibility criteria would be enrolled within first week of life, after obtaining written informed consent from the parents of the infant. Randomization in 1:1 ratio, stratified by site, sex and birth weight would be done through an interactive web response system (IWRS) using a standard web browser and email service Vivomixx R a probiotic containing a mix of 8 strains of bacteria, in a suspension form standardized to deliver 10 billion CFU/ml, or an organoleptically similar placebo would be fed to enrolled infants in a 1ml/day dose for 30 days. The follow-up of enrolled infants would take place as per a pre-specified schedule for recording morbidities and outcome assessments at the six participating sites. Screening for morbidities would be conducted by trained field workers in the community, and sick infants would be referred to designated clinics/hospitals. A physician would examine the referred infants presenting with complaints and clinical signs, blood samples would be collected from sick infants for diagnosis of neonatal sepsis by performingsepsis screen and blood culture. Appropriate treatment would be provided as per hospital protocol. Study would be implemented as per the MRC guideline for management of Global Health Trials in accordance with ICH-GCP and Indian Regulatory guidelines. A Contract Research Organization would be enaged for comprehensive monitoring and quality assurance. . The final analysis would be conducted in a blinded manner as per the statistical analysis plan (SAP) to estimate the primary outcomes sepsis, possible serious Bacterial Infection (PSBI) & secondary outcomes. The codes will be broken after DMEC permission. The protocol has been reviewed by the Research Ethics Committee of the Liverpool School of Tropical Medicine (REC-LSTM), from Research Ethics Committees of the six subject recruitment participating sitesDiscussion: This adequately powered and well-designed trial would conclusively answer the question whether probiotics can prevent neonatal sepsis in the high risk group of Low Birth Weight infants as indicated by a pilot study in 1340 LBW infants, evidence from systematic reviews of hospital based studies and a primary study on healthy newborns in Orissa. Results of the study would be generalizable to India and other Low–middle income countries.Trial registration: The study is registered at the Clinical Trial Registry of India (CTRI; 1 http://ctri.nic.in); Number CTRI/2019/05/019197, date 16 May 2019).
BackgroundAfter establishing safety and immunogenicity of Biological E’s CORBEVAX™ vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study.MethodsThis is a phase-2/3 prospective, randomised, double-blind, placebo controlled, study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX™ vaccine in children and adolescents of either gender between <18 to ≥12 years of age in Phase-II and <18 to ≥5 years of age in Phase-III with placebo as a control. This study has two age sub groups; age subgroup-1 with subjects <18 to ≥12 years of age and age subgroup-2 with subjects <12 to ≥5 years of age. In both age sub groups eligible subjects (SARS-CoV-2 RT-PCR negative and seronegative at baseline) were randomized to receive either CORBEVAX™ vaccine or Placebo in 3: 1 ratio.FindingsThe safety profile of CORBEVAX™ vaccine in both pediatric cohorts was comparable to the placebo control group. Majority of reported adverse events (AEs) were mild in nature. No severe or serious AEs, medically attended AEs (MAAEs) or AEs of special interest (AESI) were reported during the study period and all the reported AEs resolved without any sequelae. In both pediatric age groups, CORBEVAX™ vaccinated subjects showed significant improvement in humoral immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing antibody (nAb)-titers against Ancestral Wuhan and Delta strains. Significantly high interferon gamma immune response (cellular) was elicited by CORBEVAX™ vaccinated subjects with minimal effect on IL-4 cytokine secretion.InterpretationsThe safety profile of CORBEVAX™ vaccine in <18 to ≥5 years’ children and adolescents was found to be safe and tolerable. The adverse event profile was also found to be acceptable. Significant increase in anti-RBD IgG and nAb titers and IFN-gamma immune responses were observed post vaccination in both pediatric age sub groups. Both humoral and cellular immune responses were found to be non-inferior to the immune responses induced by CORBEVAX™ vaccine in adult population. This study shows that CORBEVAX™ vaccine is highly immunogenic and can be safely administered to pediatric population as young as 5 years old.The study was prospectively registered with clinical trial registry of India-CTRI/2021/10/037066
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