Every second, someone in the world is infected by the tuberculosis (TB) bacillus. Some 90-95% of those infected will never actually develop the disease, since their immune system will be able to successfully fight the bacteria responsible for it. But on average more than 10 million people still contract TB every year (10.4 million in 2015, according to the World Health Organization (WHO)). TB is one of the top ten causes of death worldwide. In 2015, 1.8 million people died from the disease, 400,000 of whom were also HIV positive. Over 95% of TB deaths occur in low- and middle-income countries, including some of Europe's neighbors.
About one-third of the world's population is currently infected with TB. Just 22 countries account for 80% of all cases worldwide. The number of multidrug-resistant TB cases at global level is thought to be close to 500,000, 10% of which are extensively drug-resistant strains.
Nearly 2.7 million TB cases occur in Sub-Saharan Africa each year. This figure is rising rapidly as a result of the AIDS epidemic that is particularly affecting this region. Each year, almost 6.3 million cases of TB are reported in Asia. In France, there are almost 5,000 new cases and approximately 900 deaths from TB each year. French Guiana, Mayotte and Ile-de-France (Greater Paris) are the regions with the highest notification rates (source : Santé publique France 2015, 2013 data).
Tuberculosis is a contagious disease caused by Koch's bacillus (strains of the Mycobacterium tuberculosis complex). This infectious agent is spread through the air via bacteria-laden droplets produced when TB patients cough. Individuals can be infected by inhaling just a few of these contaminated droplets. A person with active but untreated tuberculosis can infect an average of 10 to 15 people a year. Over the past 40 years, population movements (international travel, refugees, homeless people in industrialized countries) have largely contributed to the worldwide spread of the disease.
In 2013 in France, the notification rate for TB was much higher among homeless people (166.8 cases per 100,000 population) and prisoners (91.3 cases per 100,000 population) than in the overall population (7.1 cases per 100,000 population) (source: Santé publique France 2015).
Not everyone infected by Koch's bacillus will go on to develop TB; only 5 to 10% will progress to active TB. The bacillus can survive in a dormant state in the human body for years. Immunodeficient patients, especially those with HIV, are at greater risk of developing tuberculosis once infected. HIV and Koch's bacillus form a lethal combination, with each infectious agent boosting the other's progress. TB is the leading cause of death among HIV-positive people: it is responsible for a third of deaths among HIV patients worldwide and 40% in Africa.
In the 1940s, there were no drugs available to treat tuberculosis. Today a combination of antibiotics is used to treat the disease, but the treatment must be taken for at least six months (and up to two years). Incomplete or erratic treatment can lead to the emergence of antibiotic-resistant TB, which can then spread among the community. If treatable, these resistant TB cases are a hundred times more expensive than TB cases that can be treated using conventional therapy.
In 2016, WHO approved the use of a shorter regimen (nine months) that is much less expensive than the previously recommended treatment (which lasted up to two years for some cases of multidrug-resistant TB (MDR-TB)) – except for cases of extensively drug-resistant TB (XDR-TB) or TB that is resistant to second-line drugs. In these latter cases, a longer regimen is needed, combined with other drugs and also with new molecules (bedaquiline or delamanid).
New weapons to fight bacteria
The BCG is not a fully effective vaccine: although it is very useful for preventing severe forms of TB in young children (it is almost 90% effective against tuberculous meningitis), it only protects adults 50% of the time. It therefore cannot prevent transmission of the disease or eradicate the global epidemic. We are currently witnessing a concerted effort to develop new TB vaccines, and several phase I and II clinical trials are under way in Europe, the United States and South Africa.
At the Institut Pasteur
Several teams of microbiologists, immunologists and geneticists are developing research programs to further our understanding of host-bacillus interaction (especially using genomics tools), investigate the genetic evolution of the bacillus, improve TB diagnosis, elucidate the dynamics of antibiotic resistance and identify new TB drugs and vaccines.
Some of this research is carried out as part of large-scale European projects, including:
- TBVAC2020 for the development of new vaccines (partner Prof. Roland Brosch),
- PreDiCT-TB, funded by the Innovative Medicines Initiative (IMI), to devise new treatment combinations (partner Prof. Roland Brosch),
- NAREB (nanotherapeutics for antibiotic resistant emerging bacterial pathogens), a 2014-2018 research program coordinated by the Institut Pasteur (Prof. Brigitte Gicquel) to improve the treatment of MDR TB by using nanotransporters for therapeutic molecules.
A tuberculosis network brings together around ten institutes in the Institut Pasteur International Network which are actively involved in national programs for combating tuberculosis in various countries. Some member institutes (such as Bangui, Cambodia and Shanghai) are also leading research themselves, especially on MDR TB.
Finally, in line with its education activities, the Institut Pasteur runs a course, "Tuberculosis – biology of microorganisms", with teaching by international experts. The course is geared towards doctors, veterinarians, directors of clinical mycobacteriology laboratories, pharmacists and scientists wanting to learn about the latest developments in tuberculosis research and the use of molecular methods for diagnosis, drug susceptibility testing and epidemiology. The course was developed in Shanghai in 2008 and has since been taught in Paris, Tunis and Yaoundé.
The Institut Pasteur teams working on the topic
- Structural Biochemistry Unit
led by Pedro Alzari
- Mycobacterial Genetics Unit
led by Brigitte Gicquel
- Human Evolutionary Genetics Unit
led by Lluis Quintana-Murci
- Integrated Mycobacterial Pathogenomics Unit
led by Roland Brosch
- Microbial Individuality and Infection five-year group
led by Giulia Manina