Q: Is tuberculosis (TB) still a raging global infectious disease?
Unfortunately and shockingly, 1.6 million people died from TB in 2021 and it may have overtaken COVID-19 as the biggest killer among infectious diseases.
A quarter of the world’s population is estimated to have been infected with TB-causing bacteria, Mycobacterium tuberculosis (Mtb), of which about 5–10 percent go on to develop active TB, which can be fatal without treatment. Mtb can be controlled by the immune system within granulomas in the lungs and this is why the infected person may show no symptoms. However, if the immune system is weakened by another infection, diabetes, malnutrition, or other trauma, the Mtb can escape into the lungs and disseminate to other organs.
The challenge is determining who is at risk of active TB disease. Although the majority of those infected live in the global south, there can be ”hot spots” in any country that are centers of immigration or deprivation. In addition, with the global focus shifted to COVID-19,there is a backlog of untreated diseases in our communities.
Q: How is TB diagnosed currently?
TB is treatable with antibiotics, but the current tests often don’t detect active disease early enough to initiate treatment before the person becomes infectious. Moreover, TB in children is particularly difficult to diagnose.
The WHO recommends using rapid molecular diagnostic tests, such as the Xpert® MTB/RIF Ultra and Truenat MTB assays. These require a sample of sputum from the lungs, which can be difficult for children and vulnerable adults to produce.
The tuberculin skin test (TST) and interferon-gamma release assay (IGRA) can also be used to detect people with advanced infection, where the body has produced an immune response.
Q: Why do we need better diagnostics?
Mtb is slow-growing and has a thick cell wall, so it is difficult to extract the DNA for PCR analysis. Although sputum culture is considered a gold-standard test, it can take up to six weeks to get a definitive result. Another disadvantage is that up to 50 percent of patients don’t produce sputum and they may require a bronchial lavage—an unpleasant and invasive procedure.
The IGRA and skin tests measure the immune response but not the presence of the pathogen, and therefore, can’t differentiate between historical disease that the body has successfully overcome (and therefore, doesn’t require further treatment) and active disease that warrants treatment.
Q: How do “phage-based” diagnostics work?
Phage-based diagnostics use the inherent ability of bacteriophage to target and infect specific bacteria in a blood sample. A phage is specific to a particular strain of bacteria. The right phage can infect live Mtb, penetrate the waxy coat, and take over mycobacterial replication machinery to create hundreds of copies of the original phage. After this rapid infection, the phage breaks open the Mtb cell wall, releasing the bacterial DNA for identification with a PCR test.
Q: What is unique about phage-based diagnostics?
Unlike immune response diagnostics, phage-based diagnostics can identify the presence of live mycobacteria at an early stage of infection, offering the potential to break the cycle of infection. Live, viable Mtb present in blood is an indication that the body’s immune system has not controlled the infection and the person has active TB that needs antibiotic treatment.
This information is highly beneficial to the clinician as it enables targeted treatment and prevents patients from developing antibiotic resistance due to the inappropriate use of antibiotics in the absence of active TB.
Clinicians may also use phage-based diagnostics to make decisions on when to initiate and terminate treatment and also to monitor its efficacy.