Short course chemoprophylaxis with rifampicin, isoniazid and pyrazinamide for tuberculosis evaluated in gold miners with chronic silicosis: A double-blind placebo controlled trial

Setting: A medical facility for approximately 90 000 gold miners employed on 24 South African gold mines. Objective: To evaluate the effectiveness of rifampicin, isoniazid and pyrazinamide given for 3 months for the prevention of tuberculosis in men with silicosis. Design: A randomised double-blind placebo controlled trial with active 4-year follow up of subjects by routine radiographic screening. Results: A total of 382 gold miners with silicosis were randomised to receive rifampicin 600 mg, isoniazid 400 mg and pyrazinamide 1.25 g daily as Rifater(R) or a placebo. These men have been followed for 4 years since the end of the treatment period. Eleven men who received the combination tablet and 15 men who received the placebo tablet have developed tuberculosis (chi(2) dfl = 0.66, P = 0.4). Conclusion: This multi-drug short course chemoprophylaxis regimen has failed to prevent tuberculosis in miners with silicosis. Even if a larger study had demonstrated a statistically significant effect of the regimen as compared with placebo, the rate of tuberculosis in the men who received the three-drug regimen was unacceptably high.