Chemoprophylaxis in inactive tuberculosis: long-term evaluation of a Canadian trial

A trial of chemoprophylaxis to prevent reactivation of tuberculosis in persons with inactive disease who had never had adequate chemotherapy was conducted in Canada in the mid-1960s. Preventive drug treatment consisted of either isoniazid (INH) alone or INH plus para-aminosalicylic acid (PAS), for a maximum of 18 months. Long-term evaluation in 1974 of 1571 treated patients and 834 control patients demonstrated clearly the substantial and sustained value of adequate chemoprophylaxis in reducing the risk of reactivation. Among those who took INH alone for 6 months or more the annual reactivation rate was 1.2 per 1000 persons, while among those who took INH plus PAS the rate was 0.38/1000. These rates were, respectively, 70 and 90% less than the average rate in the controls, 3.9/1000. Among those who underwent chemoprophylaxis for less than 6 months the annual reactivation rate was 3.7/1000, similar to that in the controls. Cost-benefit analysis showed chemoprophylaxis to be economically sound. Despite the recent increasing application of this preventive measure, there are still many persons living in Canada who could benefit substantially from a course of chemoprophylaxis.