TB diagnosis remains one of the key challenges in managing this infectious disease caused by the bacterium Mycobacterium tuberculosis. The disease is transmitted through the air and primarily affects the lungs, although it can also involve other organs. It is most prevalent in low- and middle-income countries (LMICs), where socioeconomic factors and limited access to healthcare services facilitate its spread.
Early detection of the infection is essential to reduce transmission and initiate treatment promptly. For this reason, one of the primary goals of current research is to develop diagnostic tests capable of identifying the bacterium in the early stages, before the disease becomes clinically apparent.
UniSR, recently designated as a WHO Collaborating Centre for tuberculosis, is actively engaged in the development of new diagnostic strategies.
"Diagnostic tests such as QuantiFERON, a blood test, or the new skin tests currently available can tell you whether a person has already encountered the bacterium and mounted an immune response against it. However, they cannot tell you whether the bacterium is still present, which means we have no way of knowing whether or when a potentially infected individual will go on to develop the disease," explains Dr Daniela Maria Cirillo, Head of the Emerging Bacterial Pathogens Unit.
Another major challenge in TB diagnosis is the development of immunological and molecular tests that can provide early detection of active disease and identify drug-resistant forms, so as to guide effective treatment rapidly and reduce transmission. Among the goals of TB research is the timely identification of both symptomatic and asymptomatic patients. Tuberculosis can, in fact, remain asymptomatic, making it even harder to detect.
For these reasons, one of the key activities at the UniSR tuberculosis centre involves developing advanced diagnostic tests capable of detecting the bacterium even in the early, asymptomatic stages of infection — when the pathogen is microbiologically detectable but clinical manifestations have not yet appeared.
Among the tests that Dr Cirillo and her team are currently developing is a face mask similar to those used during the COVID-19 pandemic, fitted with a membrane designed to collect exhaled breath condensate — the tiny droplets expelled during breathing. The collected sample is then subjected to molecular testing capable of "reading" the genetic material present and identifying sequences specific to the tuberculosis bacterium.
"In the future, this approach could also be used to identify other pathogens beyond the tuberculosis bacterium, including as yet unknown agents and seasonal viruses such as influenza. This could help monitor the spread of epidemic diseases on a global scale," Dr Cirillo adds.
The exhaled breath test, however, is not yet sensitive enough on its own to determine whether the mycobacterial strain detected is also resistant to the drugs commonly used in TB treatment.
One of the factors slowing progress towards the elimination of the disease is precisely multidrug resistance. Specifically, tuberculosis is classified as multidrug-resistant TB (MDR-TB) when the bacterial strain responsible for the infection is resistant to treatment with the antibiotics rifampicin and isoniazid.
Resistance to anti-tuberculosis drugs can typically be diagnosed using traditional methods that assess the ability of bacteria to grow in the presence of antibiotics. In the case of tuberculosis, however, these tests are very time-consuming and sometimes lack precision. Rapid, simple and automated molecular methods also exist for testing resistance to certain specific drugs, alongside more complex tests for others. The optimal solution, however, is sequencing using Next Generation Sequencing (NGS) techniques.
"The WHO recommends NGS sequencing tests — advanced sequencing assays — to identify multidrug-resistant forms of tuberculosis. However, this type of analysis generally requires a larger sample volume than can be obtained from exhaled breath alone. Despite this, as a tuberculosis research centre we will nevertheless attempt to design tests that can work with these types of samples, while acknowledging that the results may not be fully accurate," Dr Cirillo explains.
Finally, an important goal of current research into TB diagnosis is to contribute to the development of catalogues of newly identified genetic mutations in Mycobacterium tuberculosis that confer drug resistance. Dr Paolo Miotto, Deputy Director of the UniSR Tuberculosis Centre, has been dedicated to this work for years.
Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It is transmitted primarily through the air, via respiratory droplets released by an infected person when coughing, speaking or sneezing. Transmission is more likely in enclosed, crowded environments, particularly where ventilation is inadequate.
TB diagnosis is the process by which the presence of infection or active disease caused by Mycobacterium tuberculosis is identified, using immunological, molecular and microbiological tests.
The main tests include blood tests such as QuantiFERON, skin tests and other immunological assays, as well as molecular tests designed to detect the bacterium's genetic material. Researchers are currently working to develop new tests capable of identifying the bacterium in the early stages of disease, including in asymptomatic patients.
No. Some tests only indicate that a person has come into contact with the bacterium, but do not reveal whether the infection is active or will progress to disease.
Through molecular testing and genetic sequencing (NGS), which can detect mutations associated with drug resistance.