A phase III cluster randomised placebo-controlled trial to assess the efficacy of preventive therapy in child and adolescent contacts of MDR-TB Context of research: To become sick with tuberculosis (TB), someone must first be exposed to someone who is coughing, become infected and then develop the disease. People with HIV and young children are more likely to develop TB disease once they are infected. One way to prevent TB is to find the people who live in a home with someone who has TB, check them and treat those with TB infection. This will prevent them from getting sick with TB disease. Many studies have shown that a drug called isoniazid (INH) reduces the risk of developing TB when given after being coughed on, so World Health Organization (WHO) advises giving INH to HIV-infected people and children under age 6 for six months when they have contact with someone with TB.  Right now it is unclear what medicine we should give a child who has been exposed to someone with multidrug-resistant (MDR)-TB, when the germ is resistant to the most commonly used TB medicines, like INH. MDR-TB is becoming more common.  The WHO estimated that there were more than half a million cases worldwide in 2012. Worldwide, it is estimated that at least a million children are exposed to MDR-TB every year. With new tests to diagnose TB quickly that can also detect resistance to the common TB medicines, the number of adults who are diagnosed with MDR-TB cases is increasing. In turn, the number of children exposed to MDR-TB is also increasing.   Treating children who become sick with MDR-TB takes a long time (usually 18 months), usually needs a hospital stay, has medicines that may have many side effects, and is expensive.  For these reasons, preventing MDR-TB in children is therefore very important.  Until now, there have been no big and well designed studies to help us decide if using medicine to prevent a child with contact with someone with MDR-TB from becoming sick works. A few studies where doctors treated patients who have been in contact with MDR-TB have been done, but, each of them had problems. We think medicine to prevent MDR-TB might work, but a better type of study, a randomised control trial, needs to be done to prove that it works before we can be sure. Aims and objectives: We want to do a study in South Africa that looks at people living in the homes of someone with MDR TB disease. We will use a drug that doctors already use to treat MDR-TB called levofloxacin (LFX). We will test whether this medicine, given every day for 6 months, can prevent children from getting TB and/or dying. We will include children who live with someone with MDR-TB in the study.  Children who get the medicine will be compared to those who get a sugar pill or placebo. This sugar pill looks like LFX but has no active medicine.  Children will be followed for 24 months to make sure they do not get TB or have any side effects.  We will also check if the medicine was easy to take, if it was safe, or if the TB became resistant to the LFX.  We will also check how expensive it is to give this kind of medicine in the way that we think it should be given.  Some children and their families will be asked to talk about their experience of the study and the medicine with the clinic staff. Potential applications and benefits: Until doctors learn what treatments work for preventing MDR-TB in children, it will hard to tell families what to do.  If the medicine we are testing works to prevent MDR-TB, and is safe, and acceptable to families, we will be able to tell other doctors how to decrease MDR-TB all over the world. TB programmes will also benefit from this research because fewer children will get a disease which is costly to treat. Most importantly, if this medicine works, this study could greatly benefit children exposed to MDR-TB. 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.