Whole genome sequencing for the rapid prediction of drug susceptibility in patients with suspected multi-drug resistant tuberculosis in Vietnam Mycobacterium tuberculosis is a bacteria that causes tuberculosis, an infectious disease that kills nearly 2 million people each year worldwide. Despite the availability of effective drug treatment for more than 50 years, and coordinated global efforts to control the disease, tuberculosis kills more people than any other infectious disease. One of the major reasons for the world's failure to control tuberculosis, and why it poses such a threat for the future, is that the bacteria are becoming increasingly resistant to the drug treatments. This problem is compounded by the difficulty in detecting drug resistant bacteria, which grow very slowly in the laboratory and require special facilities to handle and test safely. The current standard methods for detecting tuberculosis drug resistance take 8-12 weeks to give results and are only available in specialist laboratories. In Vietnam, for example, which has >100,000 people with tuberculosis each year, there are only two laboratories in the country that can perform full tuberculosis resistance testing. The inadequacy and inaccessibility of currently available resistance detection methods means people with drug resistant tuberculosis are either diagnosed late, or not at all, which leads to more severe disease, on-going transmission of the infection to others, and more tuberculosis deaths. This problem is especially serious if a patient has so-called 'multi-drug resistant' (MDR) tuberculosis. MDR tuberculosis is defined by resistance to at least two of the most active 'first line' anti-tuberculosis drugs. It is much harder to treat, requiring four or five 'second line' drugs that are less effective than the 'first line' treatments and must be given for 12 months or more. Ideally, resistance testing would help doctors select the best drugs to treat people with MDR tuberculosis quickly and easily and thereby ensure the patient gets better faster. However, the current resistance detection methods are too slow (and are often unavailable) to help doctors and their patients. Our proposal will investigate a new solution to the problem of tuberculosis drug resistance testing. The team from the University of Oxford in the UK have been at the forefront of using the bacteria's genetic code (or DNA) to detect resistance against all anti-tuberculosis drugs. They have developed relatively simple methods that are able to look at the whole genetic code of a bacteria (or 'whole genome sequence') and rapidly predict whether or the not the bacteria are resistant to any or all of the anti-tuberculosis drugs by detecting the genetic mutations associated with resistance. These methods take a couple of days, not the 8-12 weeks of the current standard methods, and are so accurate that Public Health England now uses them in their routine service. Other developed countries are set to follow suit, but these genetic methods have yet to be tested in less well-resourced countries like Vietnam.  Our research team will develop 'whole genome sequencing' tuberculosis resistance testing in Vietnam's national tuberculosis reference laboratory in Hanoi. We will investigate whether the method can rapidly and accurately predict susceptibility or resistance to all anti-tuberculosis drugs from a culture of the bacteria, or directly from patients spit. We will do so in patients who are strongly suspected to have MDR tuberculosis. We will also investigate whether the method can be used to predict new drug resistance in patients who are failing treatment for suspected drug susceptible tuberculosis. In all these cases, we aim to provide proof-of-principle that the new method will give rapid and accurate results that will ultimately improve the way patients are treated. We will also assess the economic benefits of the new approach.  We hope that the information provided by the project will help support the future adoption of genetic resistance detection into Vietnam's tuberculosis treatment and control programme. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.