Tuberculosis (TB) is a highly contagious disease that can damage the lungs or other parts of the body and cause serious illness. TB has killed millions of people throughout history. Anyone living in the 19th century would have lost a family member or a close friend to the disease, which once killed one in three people in London or New York.

The development of antibiotics in the 1950s, the bacille Calmette-Guérin (BCG) vaccine and improved hygiene have helped control the spread of TB. Yet today, despite the common belief that TB is under control, more people are dying of the disease each year than at any other time in history. Someone dies from TB every 15 seconds, and the epidemic is growing. Each year, TB kills approximately 2 million people. Between 2002 and 2020, the World Health Organization (WHO) predicts that 36 million people will die from TB infection.

TB can infect any part of the body. In most cases, it affects the lungs. The bacterium slowly destroys the lung tissue. At first, an infected person may suffer no more than a dry, irritating cough. The cough becomes progressively worse and can damage blood vessels, causing people to cough up blood. Other symptoms include weight loss and night sweats. In severe cases, where much of the lung has been destroyed, people become breathless and complain of chest pain.

Despite effective drugs and the BCG vaccine, one-third of the world’s population is infected with TB. In recent years, these numbers have shot up dramatically in developing and industrialized countries. About 2 million TB cases per year occur in sub-Saharan Africa where the HIV epidemic is accelerating the spread of TB. About 3 million TB cases per year occur in Southeast Asia and more than a quarter of a million are in Eastern Europe.

In almost every case, tuberculosis can be cured. TB therapy usually consists of a cocktail of up to four antibiotics taken daily for six months or more. The World Health Organization recommends a combination of isoniazid, rifampicin, pyrazonamide, ethambutol and streptomycin. Drug regimens are very effective if taken correctly. But treatment can be long and complex, so patients don’t always adhere to treatment. Many patients start to feel better soon after taking antibiotics, so they fail to complete the full course of antibiotics. This contributes to the development of drug-resistant bacteria. There is a vaccine against TB and it has been a key player in fighting the disease. But it is not ideal. The protection BCG vaccination provides varies dramatically. And the vaccine has a crucial shortcoming: after 10 years, its protection wanes, leaving adults vulnerable to attack.

Only 50 years ago, there were no drugs to cure TB. Today, strains have emerged that can resist all major anti-TB drugs. These drug-resistant strains threaten to turn TB once again into an incurable disease. TB therapy may be effective, but it is also problematic. Not only does the treatment last between six months and two years, but also the drugs may cause side effects including sickness and vomiting, rashes and flu-like symptoms. Because many patients feel better in the first weeks after starting therapy, they stop taking their medicines. But by stopping treatment, patients with TB may develop a drug-resistant form of the disease. The result is a particularly dangerous form of bacterium, the multidrug-resistant TB (MDR-TB). Already strains have been found that resist the two most powerful anti-TB drugs. MDR-TB can be cured but it is difficult to treat. Treatments for MDR-TB are more expensive and toxic than drug-susceptible TB.

TB is caused by infection with germs called Mycobacterium tuberculosis, first identified in 1882 by Robert Koch. TB can also infect cattle. This infection is caused by a similar type of bacterium called Mycobacterium bovis. It is believed that tuberculosis in humans has existed since cattle were domesticated about 10 000 years ago. TB germs from cattle can be transmitted to humans through drinking heavily infected milk. Milk-borne TB is now rare, as Western farmers have virtually eliminated the disease from their herds and pasteurization eliminates any residual bacilli.

People of all ages and nationalities can get tuberculosis. It would be a mistake to think that developed countries are spared. After a century in decline, TB is making a worrying comeback in London and New York. Each year, more than 25 000 people in the US get tuberculosis. About 3 700 of these people live in New York City. The number of people travelling in airplanes has risen dramatically over the past 40 years. TB travels with them. In many industrialized countries, at least half of TB cases are in foreign-born people. The number of refugees and displaced people in the world is also growing. TB spreads like wildfire in crowded refugee camps and shelters, and as many as 50 percent of the world’s refugees could be infected with TB. As they move, they spread TB.

TB spreads when people who have active TB sneeze, cough or speak, propelling germs into the air. All it takes is for a healthy person to inhale one infectious particle to become infected. People with active TB – i.e., those who have symptoms – can infect 10-to-15 people in one year. To breathe in TB germs, however, you need to have close, day-to-day contact with an infected person. That is why most people get TB germs from someone with whom they spend a lot of time, like a family member, friend or close coworker. People with a healthy immune system are not likely to get the disease. Only one in 10 healthy people who are infected with the bacteria will develop TB. The risk, however, is greater in babies and young children, the elderly, and people who are malnourished. People with weakened immune system, including organ transplant recipients, cancer patients receiving chemotherapy and people with HIV or AIDS, have a greater risk for catching TB. There are people who remain infected but do not have symptoms. The bacteria can lie dormant for many years. The organisms do not grow, but they are still alive. As soon as an opportunity crops up – in old age, or when a person is weakened by another disease – the bacteria reawaken and cause tuberculosis.

HIV leaves the body defenseless against the bacteria. This means that people who are HIV-positive are more likely to become infected or reactivate a latent TB infection. In Africa, incidence of TB has rocketed in the last 10 years. HIV is the most important reason why. TB is also the main killer of AIDS patients because their immune systems are so weak.

Novartis recognizes that there is an urgent need to improve existing treatment for TB and to find new medicines for drug-resistant TB that are ravaging developing countries. Our goal at NITD is to apply new genomics and bioinformatics technologies to develop novel treatments for multi-drug resistant TB. Any resulting drugs will be available without profit in those developing countries where the disease is endemic. NITD researchers plan to take advantage of the genome sequence of the Mycobacterium tuberculosis, which has been available for almost 10 years. Every piece of information on what makes this bacterium tick is contained within this sequence. The challenge is to use this newly gained knowledge to identify vulnerable parts of the organism that could be targeted by small molecules. Those small molecules can then be further refined to produce clinical drug candidates.