Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction

A Randomised, Controlled Trial to Determine if BCG Immunisation at Birth Reduces Allergy and Infection in Infants

1. To determine if BCG immunisation at birth, compared to no BCG immunisation, leads to a reduction in measures of allergy and infection in the first 12 months of life.
2. To evaluate the immunological mechanisms underlying the non-specific effects of BCG by comparing markers of immunity between the BCG and non-BCG groups.

There has been a dramatic rise in allergic diseases worldwide since the 1980s. Asthma rates increased first, followed by eczema, allergic rhinitis and, more recently, food allergy - especially in infants and young children. In Australia, the prevalence of allergic disease is particularly high: up to 30% of children are affected, and eczema and asthma are among the most common chronic diseases of childhood.

Preventing allergic disease by an immunomodulatory intervention early in life would be a major advance with significant implications for individual health and public health resources. Bacillus Calmette-Guérin (BCG) immunisation is a potential intervention with an established safety profile. This vaccine has powerful non-specific effects on the cellular immune response that potentially prime host immunity away from an allergic pathway. Observational data and one small randomised controlled trial (RCT) suggest that BCG immunisation at birth leads to a substantial reduction in allergic disease - however, there is an absence of level 1 evidence.

Inclusion criteria:

• Less than 10 days old;
• English speaking mother;
• An informed consent form must be signed and dated by their parent(s) or legally acceptable representative after the nature of the study has been explained and prior to any study assessments/procedures;
• The infant's mother has screened negative for HIV during this pregnancy;
• Born no earlier than eight weeks before estimated date of delivery;
• Birth weight >1500g.
• The legal guardian expects to be able to complete four online/phone questionnaires over the infant's first 12 months of life and for the infant to be available for skin prick testing at RCH between 12-16 months of age.

Exclusion criteria:

• Any indication for BCG immunisation in the first 12 months of life including:

  • likely travel to a high tuberculosis (TB) incidence country in the first year of life.
  • Aboriginal and Torres Strait Islander babies living in parts of Australia where the incidence of TB is higher
  • newborn babies, if either parent has leprosy or a family history of leprosy
  • newborn in contact with a patient with TB.

• Known or suspected HIV infection

• Treatment with corticosteroids or other immunosuppressive therapy, including monoclonal antibodies against tumour necrosis factor-alpha (TNF-alpha) (e.g. infliximab, etanercept, adalimumab).

• Born to a mother treated with bDMARDS (e.g. TNF-alpha blocking monoclonal antibodies) in the 3rd trimester;

• Congenital cellular immunodeficiencies including specific deficiencies of the interferon gamma pathway;

• Malignancies involving bone marrow or lymphoid systems;

• Serious underlying illness including severe malnutrition;

• Medically unstable;

• Generalised septic skin disease and skin conditions such as eczema, dermatitis and psoriasis;

• Significant febrile illness;

• Mother immunosuppressed;

• Family history of immunodeficiency;

• Consanguineous parents;

• Multiple births more than twins.