In Belgium, 1,000 cases of tuberculosis are reported each year. On the occasion of World TB Day, 24 March, we ask where UCL tuberculosis research stands.
Tuberculosis is far from disappearing. Each year, 10 million people contract it and two million of them die, making tuberculosis one of the world’s major causes of death.
Belgium is not immune: one in every 10,000 have or will have tuberculosis this year. That rate is tripled in the Brussels Capital Region, owing to higher risk factors such as poverty, alcoholism and the presence of newcomers from countries where the disease is endemic.
A contagious disease
Tuberculosis is an infectious disease caused by Koch’s bacillus (Mycobacterium tuberculosis). Several forms exist. Pulmonary tuberculosis1 is far and away the most frequent (75-80% of cases) and contagious. ‘When a tuberculosis sufferer talks, coughs or sneezes, micro-droplets of saliva containing Koch’s bacilli are diffused into the air’, explains Dr Anandi Martin, a UCL biologist specialised in tuberculosis. ‘Tuberculosis is contagious as long as the sufferer is not on antibiotics.’
In most cases, tuberculosis is curable, but the treatment is lengthy and intensive. ‘The patient has to take several medications, every day, for six to nine months,’ Dr Martin says. ‘Why so long? Because Koch’s bacillus is a mycobacterium that “grows” very slowly. It won’t show up in a culture for two months. Compare that to E. coli, which appears after 20 minutes.’
Anti-tubercular drugs can induce side-effects: liver or ocular toxicity, intestinal or gastric problems (diarrhoea, etc.), which are treated with still more medicine. Not surprising, then, that some patients don’t take their treatment well, or stop it altogether when their symptoms disappear – which doesn’t mean they’re cured. This straying from treatment is unfortunately one of the possible causes of antibiotic resistance.
In 2015, of the 10 million tuberculosis sufferers, 500,000 developed a resistant form. Eastern Europe was particularly affected. ‘Lacking national screening programmes or systematic treatment protocols, for example, former Soviet bloc countries experienced the development and spread of tuberculosis resistant to several antibiotics’, Dr Martin explains. ‘We discern two levels of antibiotic resistance. Tuberculosis that resists rifampicin and isoniazid, the two most important antibiotics that are prescribed as the first line of treatment, is “multi-drug resistant” (MDR). When MDR tuberculosis resists several second-line drugs,2 it is “extensively drug-resistant” (XDR) and almost impossible to cure.’
How do resistant tuberculosis cases arise? Several scenarios are possible. The patient can be infected directly by an MDR or XDR strain. Or the Koch bacilli develop anti-tubercular drug resistance, owing to the patient’s taking the treatment incorrectly or not receiving the right antibiotic immediately. ‘The latter case is a real problem’, Dr Martin explains. ‘As long as the patient doesn’t take the right antibiotic, the disease remains contagious, particularly for close relations. Which is why we need to detect and identify resistant forms of tuberculosis as soon as possible.’
Better tests to identify resistance
MDR or XDR Koch’s bacilli present mutations on one or several genes targeted by drugs. Some of these mutations are detectable, but not all of them are known. Dr Martin and his team are developing new molecular tests. ‘These tests analyse mycobacterial DNA and can detect rare mutations that tests currently on the market cannot. Results can be obtained in a few hours and the right antibiotic prescribed immediately.’ His colleague Dr Emmanuel André is leading a study on a mutation present in one-third of tuberculosis cases observed in South Africa.
UCL tuberculosis research projects
Dr Martin, Dr André and their team are working on other diagnostic, therapeutic and logistical research projects:
- research and development of new biomarkers to detect mutations;
- development of ‘all-in-one’ or rapid tests to detect (multi)resistant mycobacteria;
- clinical studies of bedaquiline, a new drug, in collaboration with the pharmaceutical company Johnson & Johnson;
- development of information technologies allowing tuberculosis centres and laboratories to more effectively communicate and exchange data and good practices.
Such a wide array of research, it is hoped, will lead to better treatments for all forms of tuberculosis.
(1) Forms of non-pulmonary tuberculosis exist. Koch’s bacilli can attack other organs and tissues in the body: kidneys, liver, ganglions, etc.
(2) Some dozen anti-tubercular drugs exist.
A glance at Anandi Martin's bio
1992 Bachelor’s Degree in Biology, Université libre de Liège (ULg)
1993-94 Research Assistant, ULg
1994-95 Tuberculosis training, UCL Mont-Godinne Hospital
1996 Training in Education and Public Health, ULg
1996-98 Scientific Assistant, Bolivia tuberculosis programme
1999 MSF mission in Russia (tuberculosis in prison)
2000-2011 Researcher, Institute of Tropical Medicine, Antwerp
2006 PhD, Ghent University
2012-2016 Research Assistant, Microbiology Laboratory, Ghent University
Since 2011 Secretary General, EurolacTB network (tuberculosis in Europe, Latin America, Caribbean)
Since 2016 Research Assistant, Operational Manager, Microbiology Centre, IREC, UCL
The research conducted by the team of Drs Anandi Martin and Emmanuel André is funded mainly by the World Health Organisation, Johnson & Johnson, the Fondation Damien and UCL.