Study highlights: this study provided TB screening to all subjects. Those diagnosed with active TB were referred for conventional treatment; those not diagnosed with active TB were offered 9 months of isoniazid prophylaxis. The use of isoniazid reduced TB incidence during treatment, but mass screening and latent TB treatment had no significant effect on overall TB incidence control. Gold miners in Southern Africa have a high incidence of HIV and silicosis, both of which are high risk factors for TB. One study showed that isoniazid prophylaxis reduced the incidence of tuberculosis by 55%. To investigate whether isoniazid prophylaxis has the same effect on miners, a study conducted by Churchyard et al. from the Aurum Institute and the School of Public Health, University of Witwatersrand, Johannesburg, South Africa, found that isoniazid prophylaxis had no significant effect on the control of overall TB incidence. The results were published online in the January 23, 2014 issue of NEJM. The study focused on mass screening combined with intervention treatment for active or latent TB infection to assess the role of isoniazid preventive therapy in stopping TB transmission. 78,744 miners were randomized to eight intervention groups (40,981) and seven control groups (37,763). Miners in the intervention group were offered TB screening and those diagnosed with active TB were referred for treatment, while the remainder were offered 9 months of isoniazid prophylaxis. The primary study endpoint was the incidence of TB in each group at 12 months after the end of intervention treatment. The secondary study endpoint was the prevalence of tuberculosis at the end of the study. Table 1. Analysis of the overall and primary and secondary study endpoints A total of 27,126 miners (66.2%) in the intervention group were screened and 23,659 (87.2%) miners were started on isoniazid, of whom 35%-79% were given the drug for 6 months or more. The results of the study showed that the intervention treatment did not reduce the incidence of tuberculosis. The incidence rate was 3.02 per 100 person-years in the intervention group and 2.95 per 100 person-years in the control group (intervention group rate ratio 1.00; adjusted rate ratio 0.96). The prevalence ratio of TB in both groups was 2.35% vs. 2.14% and the adjusted rate ratio was 0.98. Table 2. Total community-wide efficacy of isoniazid prophylaxis: incidence and prevalence of TB Analysis of the direct effect of isoniazid prophylaxis in 10909 miners found that treatment resulted in a reduction in TB incidence (1.10 cases/100 person-years in miners treated with isoniazid, control group The incidence rate was 2.91 cases/100 person-years in the control group; the adjusted rate ratio was 0.42, but the protective effect of isoniazid was short-lived and then rapidly disappeared. The results of the study concluded that although the use of isoniazid was successful in preventing tuberculosis during treatment, mass screening and isoniazid prophylaxis did not have a significant effect on controlling the overall incidence of latent tuberculosis in South African miners. In conclusion, 9 months of isoniazid prophylaxis did not improve the overall incidence of tuberculosis in South African miners. Even though some subgroups had better efficacy, the intervention was mild and short-lived and did not change the overall outcome. In populations at high risk for TB (those with HIV infection or silicosis), continuous isoniazid prophylaxis and regimens that maximize durability of efficacy should be considered. Mathematical models may help identify drug regimens that are effective in controlling the overall incidence of TB. Findings: (i) The interventions in this study did not reduce the incidence, prevalence, or mortality from any cause of tuberculosis, and the results were different from the successful interventions in the Alaska clinical trial. (ii) Miners who received isoniazid prophylaxis had a 58% reduction in TB incidence over the 9-month treatment period, but the lasting efficacy for TB control disappeared immediately after treatment was stopped. (iii) The use of more sensitive routine screening methods, such as the automated Xpert MTB/RIF test (which detects the presence of Mycobacterium tuberculosis and rifampicin resistance), reduces the time from diagnosis of TB to initiation of treatment, thereby reducing the duration of transmission as well as the risk of transmission. ④ The rapidly diminishing protective effect of prophylaxis on individuals may be due to inadequate treatment of latent TB infection, reactivation, or the high rate of TB transmission. ⑤ Antiretroviral therapy may reduce the risk of developing tuberculosis in individuals, but efficacy at the aggregate level depends on the extent of treatment coverage and is largely determined by study entry criteria, drug uptake, durability of efficacy, and patient compliance. Early initiation of antiretroviral therapy and maximizing treatment coverage may further reduce susceptibility to HIV-associated TB. Also, enhanced dust control to reduce silicosis is critical but unlikely to have an impact on TB case notification rates in the short term. STUDY BACKGROUND: Tuberculosis is the leading cause of death among adults worldwide, with approximately 1.4 million deaths from TB in 2011. HIV infection, exposure to silica dust from ultra-deep mines, and confined working and living conditions predispose gold miners in South Africa to TB. The rising HIV prevalence (29% in 2001) has exacerbated the TB epidemic, and in 1999, the TB case notification rate among South African gold miners exceeded 4%. Although increased HIV testing rates, free antiretroviral therapy, and targeted isoniazid prophylaxis for HIV-infected miners significantly reduced the incidence of TB, the incidence of TB remained high (3%) by 2008.In a randomized clinical trial in Alaska in the 1960s, isoniazid prophylaxis reduced the incidence of TB by 55%. treatment reduced the incidence of TB by 55% in a randomized clinical trial. This prompted researchers to consider a new intervention program for gold miners in South Africa.