Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It is one of the oldest infectious diseases known to humanity and the one that has caused the most deaths throughout history. It is estimated that in the last two hundred years alone, it has claimed the lives of more than one billion people.
Although there have been advances in its diagnosis and treatment, tuberculosis continues to be a serious problem, particularly in low- and middle-income countries. In 2023, an estimated 10.8 million new cases and 1.25 million deaths were recorded, making it the leading cause of death among infectious diseases. It affects men more than women, with 65 % of cases occurring in males and 35 % in females. In Spain, around 4,000 cases are diagnosed each year. In recent years, its incidence has increased, especially in Europe and Spain. This rise is partly attributed to the COVID-19 pandemic, which disrupted diagnosis and treatment systems.
It primarily affects the lungs, although it can also spread to other organs such as the kidneys, brain or spine. Symptoms of active tuberculosis include coughing, chest pain, weakness, weight loss, fever and night sweats. It is transmitted through the air when an infected person coughs, sneezes or speaks, releasing bacteria that can be inhaled by others.
In addition to human tuberculosis, there is a variant that affects animals, caused by Mycobacterium bovis, a related bacillus species. In Spain, it affects various species of cattle and goats, as well as wild animals such as deer, fallow deer and wild boar. Animal tuberculosis can also be transmitted to humans, which poses an additional public health risk.
It is estimated that up to 25 % of the world’s population has been exposed to the tuberculosis bacillus, meaning that one in four people could have the bacteria in their lungs. However, only 10 % of those infected develop the disease. Risk factors that increase the likelihood of latent infection progressing to active disease include immunosuppression (for example, in people with HIV), malnutrition, diabetes, tobacco use and alcohol consumption. These factors, along with adverse socioeconomic conditions, explain why tuberculosis remains a disease associated with poverty.
One of the biggest challenges in the fight against tuberculosis is the lack of effective tools to prevent, diagnose and treat it. The BCG vaccine, developed in 1921, is the only one available, but its effectiveness is limited: it protects against severe forms of tuberculosis in children, but does not prevent primary infection in adults or the reactivation of latent tuberculosis. In upper-middle-income countries where tuberculosis is rare, such as Spain, the BCG vaccine has not been routinely administered since the 1980s. There are currently 14 vaccine candidates in the clinical development phase, meaning they are being tested in humans. These candidates follow different approaches, with two main strategies: preventing infection and preventing disease.
The diagnosis of tuberculosis also presents challenges. Current methods, such as the tuberculin test, chest X-rays and sputum cultures, are slow and not always accurate. Additionally, the current treatment is long and complex, requiring the administration of four antibiotic drugs for at least six months. Many patients abandon the treatment when they start feeling better after two weeks, which can lead to relapses and the development of antibiotic resistance. Although for the first time in forty years we have new drugs against tuberculosis, variants resistant to them have already emerged. These resistant forms pose a major threat, as they limit treatment options and make disease control more difficult.
In this context, research is crucial. With insights from three experts who are working in this field – Pere-Joan Cardona, Iñaki Comas and Alberto García-Basteiro – this debate will try to resolve some key issues and learn about the latest developments: Why is there so little talk about tuberculosis if it is the infectious disease that causes the most deaths worldwide? Why does it affect men more than women? Can it only be transmitted by people with symptoms? Are there clinical or epidemiological differences between strains? Can it be transmitted from animals to humans? How? How is it diagnosed? Why is the BCG vaccine no longer given to children in Spain? What treatments are available? How are they being improved? How can the diagnosis and control of resistance be improved? What are therapeutic vaccines?
Alberto García-Basteiro and his group focus their research on observational studies and clinical trials in countries with high incidence of the disease, with particular attention to vulnerable groups such as people with AIDS and children. They are currently conducting various clinical trials on new vaccines for prevention of the disease, as well as studies to assess the efficacy of new methods of detecting the bacteria that use urine or faeces instead of respiratory samples. In addition, they are developing a field epidemiological study to determine the role of asymptomatic tuberculosis in the transmission of the disease.
Pere-Joan Cardona and his team have studied the process by which latent infection develops into active tuberculosis, identifying factors such as stress and inflammation as triggers. This finding serves as a predictive marker for tuberculosis and paves the way for research into new diagnostic and treatment methods. Additionally, they are developing a therapeutic vaccine to be administered to already infected individuals, which will reduce the duration of current antibiotic treatment from six months to just three weeks.
Iñaki Comas and his team are using genomics to study the evolution of the bacterium over thousands of years and identify the determinants of its virulence, which will enable the development of more effective treatments. They are also employing genomics to analyse how and when tuberculosis is transmitted, which will enable the design of new prevention strategies. In addition, they are testing a method to predict antibiotic resistance in tuberculosis and developing a method of genomic sequencing that speeds up disease diagnosis from sputum samples, which could revolutionise the early diagnosis of resistance.
Speakers:
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Pere-Joan Cardona, head of the Microbiology Service at Germans Trias i Pujol Hospital and leader of the Clinical and Experimental Microbiology research group at the Germans Trias i Pujol Research Institute (IGTP).
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Iñaki Comas, head of the Tuberculosis Genomics Unit at the Biomedical Institute of Valencia, Spanish National Research Council (IBV-CSIC).
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Alberto García-Basteiro, associate research professor at the Barcelona Institute for Global Health (ISGlobal) and coordinator of the Tuberculosis Research Unit at the Manhiça Health Research Centre (CISM).
Moderator:
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Jessica Mouzo, journalist at El País specialized in health.
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