A randomized trial to evaluate the toxicity and efficacy of 1200mg and 1800mg rifampicin daily for 4 months in the treatment of pulmonary tuberculosis Approximately 20 million people globally are infected with tuberculosis, and about 1.5 million people die of the disease annually, i.e. one death every 20 seconds. Currently, tuberculosis of the lungs is treated with four drugs ethambutol, isoniazid, rifampicin, and pyrazinamide daily for the first two months, followed by the two drugs isoniazid and rifampicin for the next four months. This drug combination is recommended by the World Health Organisation and is used in most countries of the world.  The combination is highly effective if taken properly, but despite this about 15% patients worldwide are not cured. Factors such as patients not completing the course, missing multiple doses, or taking (or being prescribed) the wrong dose contribute to treatment failure. Although the drugs are free to patients, there is a substantial cost, in terms of time and administration, to both the patient and the treatment services. A recent study by Gospodarevskaya  et al (Int J Tub Lung Dis. 18: 810-817) has found that patients have to terminate productive/economic activities and are often forced to borrow money and/or sell assets to cover cost of treatment, which can amount to more than three-quarters of patients' income, in the last 2 months of treatment. Reducing the duration of treatment should increase the number of people who successfully complete treatment and reduce the cost to them.  A reduction could be achieved in one of two ways: using combinations of the new drugs currently under development, or by using the currently available drugs more effectively. Given the enormous cost and long time required to develop new drugs the second option is attractive. Increasing the dose of one of the currently available drugs may allow the duration of treatment to be shortened in the very near future. Three recently published Phase III trials (RIFAQUIN, ReMOX, OFLOTUB) have failed to demonstarte that treatment shortening can be achieved with the quinolones. hus, the rifamycins offer the best hope if higher doses can be shown to be safe. Rifampicin which is responsible for killing most tuberculosis bacteria, appears to be the best choice since increasing doses of rifampicin increases its ability to kill TB bacilli in vitro and animal studies. A similar result could be obtained in human tuberculosis. However, one concern would be a possible increase in unwanted serious side effects with increasing doses. Liver damage by rifampicin appears to be rare and not connected to dose size. In the RIFATOX Trial, a dose of 1200mg, in 100 patients did not increase its toxicity. The central question this trial aims to answer is therefore: does an increase in the dosage of rifampicin allow us to shorten treatment from 6 to 4 months? We are assessing whether giving double or triple the usual dose of rifampicin (1200mg, or 1800mg rather than 600mg daily) is safe and, when given for 4 months only, will result in relapse rates similar to (or better than) those found in the standard 6 month course of treatment. Patients with newly diagnosed tuberculosis of the lung, who agree to participate and have signed a consent form, will receive either the standard 6 month treatment or a 4 month treatment containing the standard drugs but with a double or triple dose of rifampicin. Treatment allocation will be random. The success of treatment in each method will be closely monitored both clinically and by regular microscopic examination of sputum, and the safety of the increased dose of rifampicin will be monitored clinically and with blood tests. If the trial is successful, it will lead to a shorter treatment course for pulmonary tuberculosis. The expected consequences would be: more patients completing the course and higher rates of cure, reduction in rates of transmission of tuberculosis with fewer people becoming infected, a reduced cost of treatment for both patients and treatment facilities and, perhaps, a reduction in the emergence of bacterial drug resistance. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.