Scientific background

What is tuberculosis, or consumption?

Tuberculosis, or TB (short for tubercle bacillus), is an infectious disease caused by a bacterium called Mycobacterium tuberculosis. In the past, the disease was also called phthisis, from the Greek 'φΘίσις' which means 'decay', or consumption, because of the extreme weight loss TB patients suffered. TB is an airborne disease, which means that it spreads through the air when people with an active TB infection sneeze or cough.

What is the history of TB?

Tuberculosis has plagued humankind throughout history and prehistory. Mycobaterium tuberculosis may have killed more people than any other microbial pathogen. It has existed for over 20,000 years and has been discovered even among Egyptian mummies. Evidence of TB is also found in the Middle Ages, when it was known as the “king’s evil” and was believed to be curable by the touch of a king. In the 18th century, TB reached epidemic proportions in Western Europe and North America, earning the nickname “White Plague.” In 1882, Robert Koch discovered that the causative agent of the disease was Mycobacterium tuberculosis. Around 1921, Albert Calmette and Camille Guérin developed a vaccine (BCG) against it and in 1944, streptomycin was the first antibiotic successfully used against the disease. The first oral mycobacterial drugs, rifampicin and isoniazid, followed.

What are the symptoms of TB?

TB symptoms include chronic cough with blood-tinged sputum, fever, breathlessness, chest pain, night sweats, fatigue and weight loss.

Does TB only attack the lungs?

Tuberculosis typically attacks the lungs (pulmonary TB) but it can also develop in areas outside the lungs (extrapulmonary TB), such as the bones and joints, the digestive system, the bladder and reproductive system, the nervous system and the lymph nodes. Extrapulmonary TB is more common in people with a weakened immune system, such as HIV patients

Why is TB hard to treat?

TB diagnosis and treatment are very complex. Diagnosis is long, with several tests usually needed to diagnose active TB, including chest X-rays, sputum samples, microscopy and culture, CT scans and biopsies. Treatment is also long, with regimens consisting of six to nine months or more of multidrug therapy. Patients can also fall ill with what is known as latent TB infection (LTBI), which means that they are infected with TB but they don’t manifest the clinical symptoms of the disease. It is estimated that one third of the world’s population has LTBI and although they don’t have active TB they may develop it in the future. The available diagnostic tools for LTBI have serious limitations in terms of both accuracy and effectiveness, thus leaving many cases undiagnosed.

Mycobacteria are naturally resistant to antibiotics due to being surrounded by a waxy coat of lipids, called mycolic acids. This waxy coat protects the bacterium and makes it impermeable to most antibiotics. This means that even after the lengthy process of diagnosis, it is still very difficult to establish which combination of antibiotics might be successful against the bacterium.

What treatments options exist today for TB?

The usual course of treatment for pulmonary TB is two antibiotics (isoniazid and rifampicin) every day for six months and two additional antibiotics (pyrazinamide and ethambutol) every day for the first two months. It may be several weeks or even months before the patient starts feeling better. Such long treatments cause implications such as increased relapse risk, serious side effects from the drugs (such as loss of appetite, nausea, dizziness, abdominal pain and blurred vision), increased risk of clinical hepatitis, especially in cases of underlying liver disease, and, crucially, treatment noncompliance. Additionally, there are strains of TB which are resistant to nearly all antibiotics used to treat TB. Patients with drug-resistant TB need to receive special medical treatment that can potentially cause more side effects, such as depression or psychosis, hearing loss, hepatitis, and kidney impairment. These patients will also be under greater risk of dying from the disease. Resistant TB treatment is extremely challenging as it is very expensive, lengthy and disruptive for the patients’ lives

When and how were the existing treatments for TB found?

Streptomycin, isolated from the bacterium Streptomyces griseus, was discovered in 1944 as the first antibiotic with proven activity against TB. The development of isoniazid followed in 1952, as the first oral mycobactericidal drug. This breakthrough would introduce combination therapy which reduced the typical therapy duration which up until then lasted for more than 18 months. The Medical Research Council (MRC) TB unit in the United Kingdom, in collaboration with the United States Public Health Service (USPHS), spent the next forty years developing the current treatment scheme consisting of isoniazid, rifampicin, pyrazinamide and ethambutol. The introduction of rifampicin in the therapeutic course in 1968 allowed treatment times to be shortened to 6 months when used in combination with pyrazinamide.

Is there a TB vaccine?

Currently there is one approved vaccine for TB, the Bacille Calmette Guérin (BCG) vaccine, developed in 1921. However, it is 70-80% effective against the most severe forms of TB, such as TB meningitis in children, and it is less effective in protecting from respiratory TB which is the most common form of the disease in adults. Also, it is not possible to receive booster BCG shots later in life. While several new vaccines are in development, none are yet approved for use. The data that we will produce with your help will shed light on the biological role of the bacterium’s defense to antibiotics, thus contributing to the efforts of developing new vaccines.

Where are resistant strains of TB coming from?

Resistant TB strains occur for a combination of reasons. The cell wall of the bacterium has a natural permeability barrier formed by mycolic acids (a class of waxy compounds) that protects the bacterium from drugs. Gene mutations in the bacterium can also lead to the development of resistant strains. Completion of antibiotic treatment in diagnosed TB cases is crucial. The long treatment times often discourage patients from completing their treatment, thus paving the way for resistance to develop. Finally, especially in developing countries, antibiotics often are scarce and of poor quality, thus contributing to the rise of resistant strains.

Where can I learn more about TB?