Because thiacetazone has been linked with serious adverse cutaneous reactions, we undertook 1 year of systematic surveillance for cutaneous thiacetazone-associated adverse reactions within the national tuberculosis programme of Tanzania. For individual cases, we collected information on age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation (toxic epidermal necrolysis, rash without necrolysis, itching without rash), and outcome (dead or alive) within 2 weeks of onset. Univariate and multivariate analyses were done of variables relevant to outcome. 1273 patients with adverse reactions were reported. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients, and 19.1% among patients with toxic epidermal necrolysis. About 60% of all adverse reactions and deaths occurred within 20 days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than reported previously, suggesting that improved management might allow retention of thiacetazone in the armamentarium of national tuberculosis programmes even where infection with HIV is prevalent.
PIP: Thiacetazone is a useful and inexpensive companion drug in the treatment of tuberculosis (TB). Its main contribution is its ability to prevent failure and relapse in patients with initially isoniazid-resistant strains. Early toxicity studies showed that the drug was generally better tolerated in East Africa than in many other countries. Thiacetazone is an essential drug in the Tanzania National Tuberculosis/Leprosy Program. Under trial conditions in Tanzania, before the HIV epidemic, adverse reactions associated with thiacetazone were uncommon. Serious, and occasionally fatal, toxic cutaneous reactions to sulphur-containing drugs in HIV-infected patients have been recognized for several years. Recently, the use of thiacetazone in HIV-infected patients has been linked with serious adverse cutaneous reactions, including toxic epidermal necrolysis. Most reports, however, concerned only patients admitted to referral hospitals, so the Tanzania National Tuberculosis Program began a nationwide one-year systematic surveillance study to determine the frequency and severity of adverse cutaneous reactions. Individual-level data were collected on each case's age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation, and outcome within two weeks of onset. The study identified 1273 patients with adverse reactions. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients and 19.1% among patients with toxic epidermal necrolysis. Approximately 60% of all adverse reactions and deaths occurred within twenty days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than previously reported, suggesting that improved management may allow the retention of thiacetazone as a weapon against TB even where infection with HIV is prevalent.