Definitions and measurement of variables

Baseline characteristics of study participants were collected by a questionnaire at enrolment into the intervention and prior to initiation of IPT. At the request of the trade unions, no HIV testing was performed for study purposes. However, use of ART as concomitant medication was asked with respect to assessing possible adverse events. HIV prevalence among miners was estimated at 29 % in 2000 [16]. IPT dispensing dates were recorded; the number of monthly refill visits was used as a proxy of adherence (≥6 defined as optimal, 6 months being a recommended duration for IPT at the time the trial was designed [17]). The end of the intended IPT period was defined as 270 days from the first prescription date and the end of the actual IPT period as 30 days from the last dispensing date.

For estimation of the TB incidence rate, the start of the risk period was defined as the date of IPT initiation (objective 1); for the risk factor analyses the risk period started at the end of the intended or actual IPT period (objectives 2 and 3).

Miners with symptoms or signs suggesting TB were investigated and treated by the mine health services. Data on these episodes were obtained from record review. Routine diagnostic workup included sputum smear microscopy and a chest X-ray. Only one mining company routinely used mycobacterial culture to evaluate all miners with signs/symptoms suggestive of TB, the others only for those with a history of prior TB treatment. However, during the study, we endeavoured, following additional consent, to collect an additional sputum sample for smear microscopy and culture, though full coverage of this was not achieved. Cultures showing only non-tuberculous mycobacteria were not considered as TB. TB diagnoses were categorised as definite (2 positive smears or 1 positive culture for M. tuberculosis, or histological evidence of TB at autopsy in TB cases only ascertained post-mortem), probable (1 positive smear or culture with unidentified mycobacteria) or possible (clinical or radiological signs and symptoms, but no or negative smear/culture results). Medical records of participants with possible TB were reviewed by senior study clinicians, masked to study arm, to arbitrate on whether to include as incident TB.

Employment records were used to determine dates of employment and reasons for leaving the workforce (including deaths). Miners who died and underwent autopsy which revealed histological evidence of TB were included as incident TB cases.

The end of the risk period was defined as the earliest of TB treatment initiation (irrespective of the method of diagnosis), termination from the workforce, death or the end of follow-up. Participants who left the workforce due to being ‘medically boarded’ (discontinuing employment for a medical reason) were all evaluated by the mine healthcare system for active TB prior to the end of employment, and we therefore assumed that none of these represented missed TB diagnoses.