opTImisation of Methods for a Human INfection Model for Group B Streptococcus
试验速览
- 阶段
- 不适用
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- The concentration of serotype-specific IgG in vaginal secretions at baseline and at two weekly intervals
研究概览
简要总结
Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis. In 2015, it was estimated that worldwide there were at least 320,000 infants with invasive GBS disease, 90,000 infant deaths and 10,000 cases of children with disability related to GBS meningitis. Maternal rectovaginal colonization with GBS is the biggest risk factor for neonatal GBS sepsis and meningitis within the first 6 days of life, with transmission of the bacteria from mother to baby occurring around the time of birth. An estimated 20-35% of pregnant women are colonised with GBS. 1-2% of neonates born to GBS-colonised women develop invasive GBS disease in the absence of intrapartum antibiotic prophylaxis (IAP).
The current strategy to prevent neonatal GBS is to give antibiotics during labour, called IAP. This has various limitations and is not easily achieved outside of high income settings. Additionally, widespread antibiotic use raises concerns about antibiotic resistance. A better approach would be a vaccine for GBS however in order to test any vaccines it would be necessary to develop a controlled human infection model whereby healthy female volunteers are artificially colonised with GBS to test the vaccines efficacy. Before developing these human infection models researchers need to better understand how women become colonised with GBS and whether antibodies in the blood and at the mucosal surfaces provide protection. This study will be observational and will test the antibody levels at the vaginal mucosa and in the blood of a group of women who are naturally colonised with GBS at the start of the study and a group who are not colonised. Investigators will follow women up over 12 weeks to observe how colonisation changes and the effect that this has on the mucosal and blood stream antibody concentrations. This will inform the development of human infection studies.
详细描述
The global burden of Group B Streptococcus (GBS) is high and represents an unmet public health need. GBS is the leading cause of neonatal sepsis and meningitis in most countries. In 2015, it was estimated that worldwide there were at least 320,000 infants with invasive GBS disease, 90,000 infant deaths and 10,000 cases of children with disability related to GBS meningitis1.
Maternal rectovaginal colonization with GBS is a prerequisite for early onset disease within the first 6 days of life, with vertical GBS transmission occurring around the time of birth2. An estimated 20-35% of pregnant women are colonised with GBS with vertical transmission occurring in approximately 50% of colonized cases3. 1-2% of neonates born to GBS-colonised women develop invasive disease in the absence of intrapartum antibiotic prophylaxis (IAP)4.
Whilst the incidence of Early Onset Disease in the USA has declined significantly following the adoption of a universal swab-based screening and IAP policy, in countries adopting a risk-based IAP strategy, such as the UK, increases in Early Onset disease burden are reported.4. IAP has limitations as a strategy for use in countries such as Uganda due to cost and access to healthcare, as well as the risk of antimicrobial resistance developing.
Given the early onset of neonatal GBS disease and the shortcomings of IAP policies, one of the best approaches to prevent GBS disease could be to use vaccination to prevent colonisation of pregnant women. The ideal model to test any GBS vaccine would be a controlled human infection model in non-pregnant women, however in order to develop this controlled human infection model researchers need to understand how host immunity affects GBS colonisation. Around 25-30% of non-pregnant women are colonised with GBS at any time and colonisation may be lost or gained over a lifetime. Prior to performing controlled human infection models, researchers need to further understand the correlation between colonisation and GBS antibody production in serum and at mucosal surfaces and researchers need to better understand how colonisation changes over time in healthy, non-pregnant women and given the observed differences in GBS disease in high and low income countries it would be useful to perform these observations in different geographical locations.
RATIONALE
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age 18-40
- •Willing to comply with study protocol requirements
- •Able to give informed consent
- •Willing not to become pregnant and use adequate contraception for length of study
排除标准
- •Latex allergy
- •Intra-Uterine Device/Intra-Uterine System
- •Presence of untreated sexually transmitted infections at baseline
- •Known Diabetes
- •Genital dermatoses
- •Diagnosis of Cervical Intraepithelial Neoplasia within past 3 years
- •Current pregnancy
- •Post-Menopausal
结局指标
主要结局
The concentration of serotype-specific IgG in vaginal secretions at baseline and at two weekly intervals
时间窗: 12 weeks
Serotype specific IgG in vaginal secretions at baseline and at two weekly time intervals will be analysed by geometric mean and median titres calculated and comparisons made by t-test or non-parametric test as appropriate. Significance is set at the 5% level.
次要结局
- Acceptability of sampling methods(12 months)
- If the concentration of GBS IgG antibody in blood and mucosa affects the likelihood of colonisation with GBS(12 weeks)
- Evaluating how many women become uncolonised over a three month period who were colonised at baseline(12 weeks)
- If we can predict colonisation from GBS IgG antibody concentration in blood and at the mucosa(12 weeks)
- Evaluating how many women become colonised over a three month period who were uncolonised at baseline(12 weeks)