Serosurveillance Study of Maternally Derived Anti-GBS Antibody (ProGreSs)

Seroepidemiology of Maternally-derived Antibody Against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda

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.

Study Overview

• Status: Active, not recruiting
• 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

• Study Type: Observational
• Enrollment (Estimated): 6000

Contacts and Locations

Study Locations

• Uganda
  • Kampala, Uganda
    • MUJHU Care Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• 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.

Description

Delivery (Birth) Cohort

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-centre level active surveillance	To establish health-centre level active surveillance for neonatal sepsis and meningitis and GBS-related stillbirths.	31 October 2020
Neurodevelopmental outcomes	To establish the neurodevelopmental outcomes of infants with GBS disease in Uganda up to 2 years of age.	31 October 2020
GBS colonisation	To determine the GBS colonisation rate and serotypes in Ugandan women at delivery	31 October 2020

Collaborators and Investigators

• Sponsor: St George's, University of London
• Collaborators: MRC/UVRI and LSHTM Uganda Research Unit; MU-JHU CARE
• Investigators: Principal Investigator: Kirsty Le Doare, Dr., St George's, University of London

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2019
• Primary Completion (Actual): April 30, 2021
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neonatal Sepsis; Infections; Communicable Diseases; Streptococcal Infections
• Other Study ID Numbers: 17.0018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No