Clinical trial NCT04549220: Serosurveillance Study of Maternally Derived Anti-GBS Antibody
Official title: Seroepidemiology of Maternally-derived Antibody Against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda
Study type: OBSERVATIONAL
Overall 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
Lead sponsor: St George's, University of London
Sponsor class: OTHER
Collaborators: name: MU-JHU CARE
name: MRC/UVRI and LSHTM Uganda Research Unit
First posted: 2020-09-16
Enrollment: 6000
Sex: FEMALE
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maternal anti-GBS antibody concentration in infants with GBS disease compared to healthy controls.
timeFrame: 31 October 2020
Secondary outcomes:
measure: Health-centre level active surveillance
timeFrame: 31 October 2020
measure: Neurodevelopmental outcomes
timeFrame: 31 October 2020
measure: GBS colonisation
timeFrame: 31 October 2020
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: MUJHU Care Ltd
Study officials:
affiliation: St George's, University of London
name: Kirsty Le Doare, Dr.
role: PRINCIPAL_INVESTIGATOR
References: