Early Versus Late BCG Vaccination in HIV-1 Exposed Infants in Uganda in Uganda

Summary

BCG vaccination may have non-specific effects (NSE) i.e., additional benefits on childhood morbidity and mortality that are separate the vaccine's effect on the incidence of disseminated tuberculosis. Though the available literature is mostly from observational study designs, and is fraught with controversy, BCG vaccination at birth, in a high risk population of HIV exposed children, may protect infants against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy, when the immune system is more mature, may offer even greater protection. The appropriate timing of BCG vaccination could therefore be up for revision. This study will therefore compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV exposed (HE) babies.

Methods: This is an individually randomized clinical trial in 4,500 HIV exposed infants. The intervention is an intra-dermal administration of 0.05 ml of BCG vaccine within 24 hours of birth while the comparator will be an intra-dermal administration of 0.05ml of BCG vaccine at 14 weeks of age.

The main study outcomes include:

1. Severe illness in the first 14 weeks of life,
2. Innate and adaptive immune responses to mycobacterial, non-mycobacterial antigens and TLR-agonists
3. Severe illness in the first 14-52 weeks and 0-52 weeks of life.

The study will be carried in two health centers and one district hospital in Uganda.

Implications: A well-timed BCG vaccination could have important additional benefits in HE infants. This trial could inform the development of programmatically appropriate timing of BCG vaccination for HE infants.

Conditions

• Severe Illness
• Septicaemia
• Diarrhoea
• Lower Respiratory Infection

Interventions

BIOLOGICAL

BCG at birth

See previous description

BIOLOGICAL

Control arm: Delayed BCG

See previous description

Sponsors & Collaborators

• University of Bergen

  collaborator OTHER

• Radboud University Medical Center

  collaborator OTHER

• Makerere University

  lead OTHER

Principal Investigators

• Victoria Nankabirwa, MD, MPH, PhD · School of Public Health, Makerere University

• Halvor Sommerfelt, MD, PhD · CISMAC, Center for International Health, University of Bergen

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

1 Day

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-07-31

Primary Completion

2024-06-21

Completion

2024-06-21

Countries

• Uganda

Study Locations