Serosurveillance Study of Maternally Derived Anti-GBS Antibody

NCT04549220 | Active Not Recruiting

• 1 other identifier: 17.0018
• Study Type: observational
• Target: 6,000
• Locations: 1 country
• Sites: 1

Brief Summary

Globally, neonatal mortality remains unacceptably high, with little change in the death rate in the first 28 days of life since 1990, despite reductions in under-5 mortality of up to 50% over the same period. In 2014, neonatal deaths accounted for 44% of all deaths in children under 5 with neonatal infection accounting for over a third of all deaths. Group B Streptococcus (GBS) is a major cause of septicemia and meningitis in infants globally and a cause of severe adverse neurodevelopmental outcomes in up to 50% of meningitis survivors. It can also lead to sepsis in pregnant women. GBS acquisition occurs through vertical transmission in 15%-50% of infants born to a vaginally/rectally colonized mother. Maternal colonization is a prerequisite for early onset (EO) and a risk factor for late onset (LO) disease. Our proposal will provide these critical data in Uganda (a country with high neonatal disease burden) in a 12 month pilot study to determine: the burden of GBS disease in a cohort of mother/infant pairs and establish an active surveillance platform for monitoring of early and late onset neonatal infection in term and preterm infants in Uganda and compare this to the burden known for other African countries. This provides essential data on GBS disease outcomes from a high-HIV burden African cohort reflecting the usual standard of care in a low income, highly deprived urban environment. This pilot study will establish minimum disease estimates in the Ugandan cohort to determine the feasibility of a cohort study over three years to determine the level of antibody against GBS in cord blood from pregnancies where women are GBS colonized and non-colonized but whose infants do not develop GBS disease in the first three months of life and compare this to the level in the blood of infants who develop GBS disease. We will compare these results with those from other African countries such as South Africa to enable a robust estimate of potential sero-correlates of protection from natural infection against the most common GBS-disease-causing serotypes.

Conditions

Group B Streptococcus Carrier in Childbirth; Group B Streptococcal Infection, Late-Onset; Group B Streptococcal Infection, Early-Onset; Group B Streptococcus Neonatal Sepsis; Group B Strep Infection

Outcome Measures

Primary Outcomes (1)

• Maternal anti-GBS antibody concentration in infants with GBS disease compared to healthy controls.

  To establish maternal anti-GBS antibody concentration in infants with GBS disease compared to healthy controls.

  31 October 2020

Secondary Outcomes (3)

• Health-centre level active surveillance

  31 October 2020

• Neurodevelopmental outcomes

  31 October 2020

• GBS colonisation

  31 October 2020

Study Arms (2)

Delivery (Birth) Cohort

All women greater than or equal (≥) to 18 years of age and emancipated minors aged between 14 and 17 years of age delivering a live infant or stillbirth at Kawempe Referral Hospital over a 6-month pilot phase will be invited to participate in the study until a sample size of at least 5000-6000 women is achieved.

Active Surveillance Cohort

This is expected to improve capacity for managing and investigating infants \<3 months of age presenting with suspected sepsis at Kawempe Neonatal Intensive Care Unit (NICU), Postnatal Ward, and Acute Paediatric Wards and Mulago Hospital Paediatric Acute Care Unit, through provision of supplies for blood culture, CSF culture and nasopharyngeal swabs. Mothers/caretakers of Neonates that are diagnosed with GBS through this active case surveillance will be invited to participate in the study and will be enrolled following written informed consent.

Eligibility Criteria

• Age: 17 Years+
• Gender Eligibility Details: Participant eligibility is based on pregnancy
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will enrol pregnant women from the general population who deliver at Kawempe Hospital and follow their infants to 90 days of age.

You may qualify if:

• consecutive mothers greater than or equal (≥) the age of 18 years delivering at Kawempe Hospital (live or stillbirth) and emancipated minors aged between 14-17 years of age,
• willing to stay in the area for the first three months of life or willing to travel to clinic until their child is 2 years old if their infant has known or presumed GBS infection).

You may not qualify if:

• Unable to give written informed consent
• Active Surveillance Cohort Matching \& Adjustment Criteria: (these will be applied at the analysis stage): (i) exposure to intrapartum antibiotic prophylaxis: defined as intravenous penicillin, ampicillin, cefazolin, clindamycin or vancomycin, for ≤2 hours before delivery. (ii) blood transfusion in the 30 days before delivery (iii) HIV status (iv) Maternal age (v) Infant gestational age

Sponsors & Collaborators

• St George's, University of London: lead
• MU-JHU CARE: collaborator
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator

Study Sites (1)

MUJHU Care Ltd

Kampala, Uganda

Location

MeSH Terms

Conditions

Streptococcal Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Kirsty Le Doare, Dr.

  St George's, University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 16, 2020
• Study Start: April 24, 2019
• Primary Completion: April 30, 2021
• Study Completion: July 30, 2025
• Last Updated: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)