Validation of the Actiphage system as a blood-based diagnostic solution for active and incipient TB

Background: Tuberculosis (TB) remains one of the leading causes of death from infectious diseases worldwide. In many infected individuals it remains dormant (latent TB; LTBI), and about a quarter of the global population, unknowingly are LTBI and hence silent carriers of TB. Around 80% of active TB cases arise from untreated latent infections, half of which are fatal without diagnosis and treatment. Delays in diagnosis are common due to misdiagnosis and low awareness among healthcare professionals and the public. This is compounded by the suboptimal use of molecular diagnostics—only 37% of cases currently have a corresponding sputum-based molecular test performed as it is difficult to obtain sputum and therefore are unsuitable for this test. This highlights the need to expand such testing beyond sputum samples. PBD Biotech have shown that phage-based testing detects only live, viable Mycobacterium tuberculosis (Mtb). In this regard, we have developed Actiphage, a unique pathogen directed phage-based diagnostic technology that can diagnose TB from blood samples. The Actiphage® test delivers results in under eight hours—compared to at least six weeks for culture methods (the current gold standard) —with exceptional specificity (>95%) and a lower detection limit (<10cells/ml) than any other live bacteria test. Aims and Objectives: This project aims to validate the diagnostic accuracy and reproducibility of Actiphage® TB in a real-world NHS setting. The Primary objective is to determine Actiphage®’s sensitivity and specificity for untreated active TB. Methods: A cross-sectional observational study will recruit 103 adults presenting with suspected pulmonary TB or acute respiratory illness at University Hospitals of Leicester. Participants will be assigned to two groups: confirmed/probable TB cases and non-TB controls. Up to 30ml of blood will be collected per participant for Actiphage® testing and comparator assays (e.g., IGRA, culture, PCR). Results will be analysed for diagnostic accuracy, reproducibility, and agreement between labs. Public and patient engagement activities will assess test acceptability. Timeline: 12 months Milestones include patient recruitment, interim data analysis, stakeholder feedback and final reporting. Knowledge Mobilisation, Dissemination and Impact PBD Biotech partners with the University of Leicester and the Leicester Respiratory NIHR Biomedical Research Centre, granting us access to state-of-the-art laboratory infrastructure and a rich reservoir of patient-derived data, enabling the continued development of our innovative diagnostic solution. Key findings will be shared through peer-reviewed publications, NHS networks, and global TB conferences. We will also reach out to beneficiaries such as clinicians, patients and pharmaceutical companies, to conduct larger clinical trials and further validate the efficacy of the solution to ensure commercial uptake and NHS adoption. The success of the project will significantly reduce TB transmission, hospital stays, and healthcare costs by enabling earlier diagnosis and achieve WHO’s End TB Strategy Objectives and UN SDGs. Research Inclusion: Our project design prioritises inclusion across gender, ethnicity, age, geography, disability, and will also target underrepresented groups often excluded from sputum-based testing and involve diverse demographic recruitment. Patient involvement has shaped study design and documentation, ensuring accessibility and acceptability.