Fighting a common and persistent killer
9 February 2018
Tuberculosis is one of the oldest infectious diseases – and still one of the deadliest. Scarce funding threatens to hamper its eradication and has given rise to the threat of multi- resistant strains that demands new approaches in fighting the disease.
Dr. Delia Goletti spends every single day fighting an infectious disease that should not – on the face of it – be difficult to defeat. It is not a new virus, like HIV was in the 1980s or SARS was two decades later. On the contrary, the disease has been around for as long as mankind, and the bacterium at its root has been known for more than a century. It does not spread as easily as measles, rubella or influenza, but without treatment, its mortality rate is similar to Ebola’s. Yet, it is a disease that often goes unnoticed. As a matter of fact, the infection is harmless for most healthy individuals. But it is one of the most common chronic infections in the world and when it does cause vague symptoms weeks to decades later – mainly cough, weight loss, low-grade fever, and fatigue – its airborne flight infects 10 others and a long and difficult drug therapy is needed to cure it. Its name? Tuberculosis (TB).
Infection or vaccination?
Available tests are currently only approved to detect two stages of the disease: latent tuberculosis infection (LTBI) and active disease (TB). A diagnosis of active TB usually requires a microbial culture and an x-ray or a biopsy, if the disease affects organs besides the lungs. As for latent infection, the tuberculin skin test (TST), or Mantoux, has long been the most common way to detect it. But the century-old test has several disadvantages: it requires two visits to the doctor, its interpretation is highly subjective and error-prone. In addition, it can’t distinguish between an infection or a previous vaccination with Bacille Calmette-Guérin (BCG). “Though the BCG vaccine is no longer common in Western countries since it offers only limited protection against TB, it is still the most common vaccination in the world,” explains Dr. Goletti. “In Africa, everyone gets vaccinated within the first week of life.”
In the early 2000s, a new laboratory blood test reached the market. Called QuantiFERON, it requires mixing some of the patient’s blood with Mycobacterium tuberculosis protein fragments. The level of the immune response in the blood sample is used to determine if the patient’s immune system knows the bacterium from prior TB infection. The QuantiFERON technology, unlike TST, is not fooled by previous immunizations and is considered to be the most accurate test for TB infection. But currently it cannot distinguish a latent infection from active disease.
That is why Dr. Goletti keeps looking for approaches that would help to further distinguish the various stages of the disease. She heads a team of seven and sees about 15 patients a week. INMI is the reference center for tuberculosis in central and southern Italy, and takes in about 300 cases a year (mostly immigrants) including rare cases of drug-resistant TB.
“We’ve been looking for antigens that cause a reaction only during the disease, as well as antigens that only show up in latent infections,” she says.“We’ve been experimenting with different readouts, test formats, biological samples – for example, trying to use urine instead of blood.”