The investigators will conduct a n=5,400 Phase 3, double-blind, individually randomised placebo-controlled clinical trial of 5 years' duration in primary schools in City of Cape Town Metropolitan Municipality, Western Cape Province, Republic of South Africa.

The primary objective of the trial is to determine whether a weekly oral dose of 0.25 mg (10,000 IU) vitamin D3, administered for three years, reduces risk of acquisition of latent tuberculosis infection (LTBI) in Cape Town primary schoolchildren.

Statistical analysis will be performed on an intention-to-treat basis to compare acquisition of LTBI in intervention vs. control arms during three-year follow-up. The primary analysis will be logistic regression with presence/absence of LTBI at follow-up as the outcome, adjusted for a random effect of school of attendance.

Inclusion Criteria:

• Pupil enrolled in Grades 1-4 of participating primary schools
• Age 6-11 years at enrolment
• Pupil gives written informed assent to participate in main trial
• Pupil's parent / legal guardian gives informed consent for pupil to participate in main trial

Exclusion Criteria:

• Age ≤5 years or ≥12 years at enrolment
• Previous positive Interferon-Gamma Release Assay (IGRA) or Mantoux test
• Previous treatment for LTBI or active TB
• Clinical signs of rickets
• History of myalgia on walking
• Inability to rise unaided from squatting position
• Taking supplemental vitamin D at a dose >400 IU daily or equivalent in the previous month
• Diagnosis of any chronic illness other than asthma
• Suspected HIV infection in child with parent or legal guardian declining to have child HIV-tested
• Use of any regular medication other than asthma medication
• Plans to move away from study area within 3 years of enrolment
• Unable to swallow one placebo softgel with ease
• Positive Quantiferon-TB Gold Plus test at screening